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Trial of MEK Inhibitor and PI3K/mTOR Inhibitor in Subjects With Locally Advanced or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT01390818
Recruitment Status : Completed
First Posted : July 11, 2011
Results First Posted : March 7, 2017
Last Update Posted : March 7, 2017
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
EMD Serono

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Locally Advanced Solid Tumor
Metastatic Solid Tumor
Breast Cancer
Non Small Cell Lung Cancer
Melanoma
Colorectal Cancer
Interventions Drug: MSC1936369B (pimasertib)
Drug: SAR245409 (PI3K and mTOR inhibitor)
Enrollment 146
Recruitment Details First subject (informed consent): May 2011. Study completion date: Apr 2015. A total of 192 subjects were screened and 146 subjects entered the trial and received the investigational medicinal product (IMP).
Pre-assignment Details Study had a 4-day Drug-Drug Interaction (DDI) period, within 1 week prior to Day 1 Cycle 1, to assess possible interaction only in selected subjects where in SAR245409 and Pimasertib were administered alone on Day 1 and Day 3, respectively.
Arm/Group Title Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily CRC: Pimasertib 60mg and SAR245409 70mg Once Daily MEL: Pimasertib 60mg and SAR245409 70mg Once Daily
Hide Arm/Group Description Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 milligram (mg) along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (Dose Escalation [DE] cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 90 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 90 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 60 mg along with twice oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 45 mg along with twice oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Subjects with relapsed or refractory metastatic triple negative breast cancer (TNBC) defined as estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) negative carcinoma of the breast with no approved therapies in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject. Subjects with a histologically confirmed diagnosis of relapsed or refractory metastatic non-small cell lung cancer (NSCLC) in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject. Subjects with relapsed or refractory metastatic colorectal carcinoma/cancer (CRC) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject. Subjects with relapsed or refractory metastatic melanoma (MEL) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Period Title: Overall Study
Started 3 3 3 4 4 3 19 14 3 3 4 26 24 18 15
Completed 3 3 3 4 4 3 19 14 3 3 4 26 24 18 15
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Arm/Group Title Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily CRC: Pimasertib 60mg and SAR245409 70mg Once Daily MEL: Pimasertib 60mg and SAR245409 70mg Once Daily Total
Hide Arm/Group Description Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 milligram (mg) along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 90 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 90 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 60 mg along with twice oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 45 mg along with twice oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort). Subjects with relapsed or refractory metastatic triple negative breast cancer (TNBC) defined as estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) negative carcinoma of the breast with no approved therapies in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject. Subjects with a histologically confirmed diagnosis of relapsed or refractory metastatic non-small cell lung cancer (NSCLC) in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject. Subjects with relapsed or refractory metastatic colorectal carcinoma/cancer (CRC) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject. Subjects with relapsed or refractory metastatic melanoma (MEL) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject. Total of all reporting groups
Overall Number of Baseline Participants 3 3 3 4 4 3 19 14 3 3 4 26 24 18 15 146
Hide Baseline Analysis Population Description
The Safety analysis set (SAF) included subjects who received at least one (non-zero) administration of the trial IMPs (pimasertib and/or SAR245409).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 4 participants 4 participants 3 participants 19 participants 14 participants 3 participants 3 participants 4 participants 26 participants 24 participants 18 participants 15 participants 146 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
  66.7%
1
  33.3%
1
  33.3%
2
  50.0%
1
  25.0%
2
  66.7%
16
  84.2%
12
  85.7%
3
 100.0%
2
  66.7%
2
  50.0%
22
  84.6%
16
  66.7%
12
  66.7%
13
  86.7%
107
  73.3%
>=65 years
1
  33.3%
2
  66.7%
2
  66.7%
2
  50.0%
3
  75.0%
1
  33.3%
3
  15.8%
2
  14.3%
0
   0.0%
1
  33.3%
2
  50.0%
4
  15.4%
8
  33.3%
6
  33.3%
2
  13.3%
39
  26.7%
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 4 participants 4 participants 3 participants 19 participants 14 participants 3 participants 3 participants 4 participants 26 participants 24 participants 18 participants 15 participants 146 participants
Female
3
 100.0%
1
  33.3%
2
  66.7%
1
  25.0%
1
  25.0%
1
  33.3%
6
  31.6%
13
  92.9%
1
  33.3%
2
  66.7%
0
   0.0%
26
 100.0%
15
  62.5%
11
  61.1%
4
  26.7%
87
  59.6%
Male
0
   0.0%
2
  66.7%
1
  33.3%
3
  75.0%
3
  75.0%
2
  66.7%
13
  68.4%
1
   7.1%
2
  66.7%
1
  33.3%
4
 100.0%
0
   0.0%
9
  37.5%
7
  38.9%
11
  73.3%
59
  40.4%
1.Primary Outcome
Title Number of Subjects With Dose Limiting Toxicities (DLT)
Hide Description DLT was defined as any of the following toxicities experienced during the first cycle of treatment at any dose level (DL) and judged not to be related to the underlying disease or any concomitant medication by the Investigator and/or the Sponsor: A treatment emergent adverse event (TEAE) of potential clinical significance such that further dose escalation (DE) would have exposed subjects to unacceptable risk. Any Grade greater than or equal to (>=) 3 non-hematological toxicity, except for: Grade 3 diarrhea, nausea and vomiting with a duration less than or equal to (<=) 48 hours despite adequate supportive care and Alopecia. Grade 4 neutropenia of > 5 days duration or febrile neutropenia. Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia. Any treatment interruption > 2 weeks due to AEs not related to the underlying disease or concomitant medication at any dose level and any severe, life-threatening impairing daily functions complication or abnormality.
Time Frame Day 1 up to Day 16 in cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The dose escalation (DE) analysis set included all subjects treated in DE cohorts who received at least 80 percent (%) of pimasertib and 80% of SAR245409 full planned doses in the first cycle (ie, 21-day period from Day 1) of treatment or who experienced a DLT during the first cycle of treatment regardless of the received amount of each drug.
Arm/Group Title Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 milligram (mg) along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 90 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 90 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 60 mg along with twice oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 45 mg along with twice oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Overall Number of Participants Analyzed 3 3 3 3 2 3 11 11 2 3 4
Measure Type: Number
Unit of Measure: subjects
0 0 0 0 0 0 0 2 1 2 1
2.Secondary Outcome
Title Number of Subjects Experiencing Any Treatment-Emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in a subject administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as those AEs that started between first dose of study drug and up to 30 days after last dose.
Time Frame Baseline up to 30 Days after last dose; assessed up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) analysis set was to include all subjects who had received at least 1 (non-zero) administration of the trial investigational medicinal products (IMPs) MSC1936369B (pimasertib) and/or SAR245409.
Arm/Group Title Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily MSC1936369B (Pimasertib) 45mg and SAR245409 50mg Twice Daily TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily CRC: Pimasertib 60mg and SAR245409 70mg Once Daily MEL: Pimasertib 60mg and SAR245409 70mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 mg along with single oral dose of 30 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 30 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 90 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 90 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 60 mg along with twice oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 45 mg along with twice oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Subjects with relapsed or refractory metastatic triple negative breast cancer (TNBC) defined as estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) negative carcinoma of the breast with no approved therapies in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Subjects with a histologically confirmed diagnosis of relapsed or refractory metastatic non-small cell lung cancer (NSCLC) in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Subjects with relapsed or refractory metastatic colorectal carcinoma/cancer (CRC) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Subjects with relapsed or refractory metastatic melanoma (MEL) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Overall Number of Participants Analyzed 3 3 3 4 4 3 19 14 3 3 4 26 24 18 15
Measure Type: Number
Unit of Measure: subjects
3 3 3 4 4 3 19 14 3 3 4 26 24 18 15
3.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Pimasertib (MSC1936369B)
Hide Description [Not Specified]
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 and 15 of cycle 1 until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 and 15 of cycle 1 until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 and 15 of cycle 1 until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 and 15 of cycle 1 until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 and 15 of cycle 1 until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 and 15 of cycle 1 until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 and 15 of cycle 1 until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 10 26 14 4 3 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: nanogram/millilitre (ng/mL)
Day 1 (n=6, 10, 26, 13, 4, 3, 25, 23, 18, 15)
86.06
(51.31 to 144.3)
188.2
(138.5 to 255.9)
246.1
(191.8 to 315.6)
406.9
(284.6 to 581.7)
83.72
(18.05 to 388.3)
232.5
(190.9 to 283.2)
323.1
(253.9 to 411.1)
295.4
(240.9 to 362.2)
245.6
(198.5 to 304.0)
234.0
(182.6 to 299.8)
Day 15 (n=6, 9,15,9, 3, 1, 16, 17, 13, 10)
131.3
(85.13 to 202.6)
212.8
(178.9 to 253.1)
234.2
(166.2 to 330.1)
516.4
(375.0 to 711.0)
143.1
(22.82 to 897.8)
NA [1] 
(NA to NA)
320.5
(286.2 to 358.9)
327.6
(248.5 to 431.9)
307.7
(205.0 to 461.8)
338.9
(281.0 to 408.8)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
4.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of Pimasertib (MSC1936369B)
Hide Description [Not Specified]
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 10 26 14 4 3 26 24 18 15
Median (Full Range)
Unit of Measure: hour
Day 1 (n= 6, 10, 25, 13, 4, 3, 25, 23, 18, 15 )
1.750
(0.50 to 2.08)
0.765
(0.50 to 2.15)
2.020
(0.50 to 8.05)
1.500
(0.50 to 3.00)
1.485
(0.50 to 2.08)
1.550
(0.50 to 2.07)
1.500
(0.50 to 7.90)
1.520
(0.50 to 7.85)
1.490
(0.50 to 4.20)
1.050
(0.45 to 4.00)
Day 15 (n= 6, 9, 15, 9, 3, 1, 16, 17, 13, 10)
1.275
(0.50 to 3.07)
1.000
(1.00 to 1.63)
2.000
(1.00 to 7.95)
1.550
(1.00 to 2.00)
2.000
(1.50 to 4.17)
NA [1] 
(NA to NA)
1.505
(0.53 to 3.00)
1.530
(1.00 to 4.00)
1.500
(0.50 to 8.00)
1.030
(0.48 to 3.83)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
5.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Last Sampling Time (0-24 Hours) of Pimasertib (MSC1936369B)
Hide Description Area under the concentration-time curve from time 0 to the last quantifiable concentration.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set . Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 10 26 14 4 3 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: hour*nanogram per millilitre (hr*ng/mL)
Day 1 (n=6, 10, 25, 13, 4, 3, 25, 23, 18, 15)
426.8
(306.2 to 594.9)
734.4
(586.1 to 920.3)
1547
(1238 to 1934)
2116
(1664 to 2692)
326.1
(110.9 to 958.7)
1252
(1100 to 1425)
1781
(1404 to 2260)
1754
(1480 to 2078)
1709
(1361 to 2146)
1093
(871.5 to 1371)
Day 15 (n=6, 9,15,9, 3, 1, 16, 17, 10, 13)
625.3
(405.7 to 963.9)
902.0
(747.6 to 1088)
1617
(1170 to 2236)
2552
(2185 to 2980)
773.1
(201.0 to 2974)
NA [1] 
(NA to NA)
2136
(1713 to 2663)
1889
(1540 to 2318)
1988
(1487 to 2658)
1506
(1141 to 1988)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
6.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of Pimasertib (MSC1936369B) at Day 1
Hide Description

Area under the concentration-time curve from time 0 extrapolated to infinity, calculated as AUC0-t + last observed concentration (Clast)/terminal rate constant (λz), using the Linear up/Log down method.

Terminal rate constant (λz).

Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "N" signifies the number of subjects evaluable for this outcome measure. Data was not available for 'Pimasertib (MSC1936369B) 60mg Twice Daily' arm as no subjects were considered evaluable because of limited number of samples collected to characterize the terminal phase rate constant needed for the calculation of AUCinf.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 9 23 13 3 0 22 22 14 13
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr*ng/mL
451.6
(319.8 to 637.8)
770.9
(599.9 to 990.6)
1607
(1237 to 2087)
2202
(1716 to 2826)
503.1
(153.1 to 1654)
1869
(1451 to 2407)
1830
(1518 to 2207)
1857
(1414 to 2437)
1113
(858.9 to 1442)
7.Secondary Outcome
Title Area Under the Concentration-Time Curve (AUC) During a Dosing Interval (Tau) of Pimasertib (MSC1936369B)
Hide Description [Not Specified]
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 10 26 14 4 3 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr*ng/mL
Day 1 (n= 6, 10, 26, 13, 3, 3, 24, 23, 17,13)
426.8
(306.2 to 594.9)
742.1
(602.0 to 914.7)
1547
(1238 to 1934)
2116
(1664 to 2692)
354.9
(48.21 to 2613)
1252
(1100 to 1425)
1882
(1513 to 2341)
1754
(1480 to 2078)
1772
(1409 to 2227)
1093
(871.5 to 1371)
Day 15 (n=6, 9, 15, 9, 3, 0, 16, 17, 10, 13)
650.4
(440.1 to 961.2)
902.0
(747.6 to 1088)
1617
(1170 to 2236)
2552
(2185 to 2980)
773.1
(201.0 to 2974)
NA [1] 
(NA to NA)
2136
(1713 to 2663)
1889
(1540 to 2318)
1988
(1487 to 2658)
1506
(1141 to 1988)
[1]
Data could not be calculated because there were no subjects evaluated for this arm at the specified time point.
8.Secondary Outcome
Title Half-Life (t1/2) of MSC1936369B (Pimasertib)
Hide Description [Not Specified]
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 10 26 14 4 3 26 24 18 15
Median (Full Range)
Unit of Measure: hour
Day 1 (n=6, 9, 23, 13, 4, 3, 22, 22, 15, 13)
6.250
(5.03 to 7.16)
4.670
(1.85 to 5.79)
4.840
(3.23 to 9.99)
4.800
(3.49 to 7.62)
3.320
(2.60 to 4.72)
4.640
(4.25 to 4.74)
4.840
(2.46 to 8.41)
4.370
(3.71 to 8.26)
4.770
(3.51 to 12.8)
4.240
(3.32 to 4.84)
Day 15 (n=6, 9, 14, 9, 2, 1, 16, 16, 9, 12)
5.855
(2.93 to 7.88)
5.410
(3.90 to 10.8)
6.755
(4.61 to 14.3)
5.590
(3.97 to 14.1)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
5.210
(3.25 to 12.8)
5.250
(4.33 to 8.65)
5.210
(4.80 to 6.94)
4.325
(3.40 to 5.96)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
9.Secondary Outcome
Title Total Body Clearance (CL/f) of Pimasertib (MSC1936369B)
Hide Description The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the Dose with area under the plasma concentration time curve from time zero to infinity (AUC0 inf)=Dose/AUC0- inf.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "N" signifies number of subjects evaluable for this outcome measure and "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 10 26 14 4 1 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: litre per hour (L/hr)
Day 1 (n=6, 10, 26, 13, 3, 0, 22, 22, 14, 13)
33.22
(23.52 to 46.92)
38.90
(30.26 to 50.00)
37.99
(29.33 to 49.22)
40.88
(31.85 to 52.47)
89.49
(27.14 to 295.1)
NA [1] 
(NA to NA)
32.12
(24.95 to 41.36)
32.75
(27.16 to 39.50)
30.75
(23.41 to 40.41)
53.94
(41.61 to 69.62)
Day 15 (n=6, 9, 15, 9, 3, 1, 16, 17, 10, 13)
23.06
(15.59 to 34.10)
33.30
(27.63 to 40.13)
37.11
(26.82 to 51.33)
35.28
(30.19 to 41.23)
58.22
(15.03 to 225.6)
NA [2] 
(NA to NA)
28.11
(22.54 to 35.07)
31.73
(25.85 to 38.94)
30.20
(22.59 to 40.38)
39.81
(30.17 to 52.52)
[1]
Data could not be calculated because there were no subjects evaluated for this arm at the specified time point.
[2]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
10.Secondary Outcome
Title Apparent Volume of Distribution of Total Pimasertib During the Terminal Phase Following Oral Administration (Vz/f) of Pimasertib
Hide Description Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Apparent volume of distribution during the terminal phase, calculated by CL/f/λz. Terminal rate constant (λz). The regression analysis (determination of λz) was to contain as many data points as possible (but excluding Cmax) and had to include concentration data from at least 3 different time points, consistent with the assessment of a straight line (the terminal elimination phase) on the log-transformed scale.Data was not available for 'Pimasertib (MSC1936369B) 60mg Twice Daily' arm as no subjects were considered evaluable because of limited number of samples collected to characterize the terminal phase rate constant needed for the calculation of Vz/f.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "N" signifies number of subjects evaluable for this outcome measure and "n" signifies the number of subjects evaluable at specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 10 26 14 3 0 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: liter
Day 1 (n=6, 9, 23, 13, 3, 0, 22, 22, 14, 13)
294.3
(218.5 to 396.4)
240.2
(202.5 to 284.9)
282.8
(227.7 to 351.4)
283.0
(224.0 to 357.6)
394.1
(146.9 to 1058)
223.8
(182.7 to 274.3)
226.9
(193.9 to 265.4)
216.2
(174.6 to 267.8)
322.0
(251.5 to 412.3)
Day 15 (n=6, 9, 13, 9, 0, 0, 16, 16, 9, 12)
188.7
(133.4 to 266.9)
261.8
(187.9 to 364.8)
396.4
(276.9 to 567.3)
302.4
(223.1 to 409.7)
NA [1] 
(NA to NA)
226.3
(189.7 to 270.1)
250.9
(214.2 to 293.9)
230.6
(169.0 to 314.6)
273.8
(213.8 to 350.7)
[1]
Data could not be calculated because there were no subjects evaluated for this arm at the specified time point because of limited number of samples collected to characterize the terminal phase rate constant needed for the calculation of Vz/f.
11.Secondary Outcome
Title Accumulation Ratio (Racc) for AUCtau of Pimasertib (MSC1936369B): Day 15
Hide Description Accumulation ratio (Racc) for AUCtau, calculated as Day 15 dosing interval AUCtau per Day 1 dosing interval AUCtau.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "N" signifies number of subjects evaluable for this outcome measure and "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 9 15 9 3 1 15 17 10 13
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
1.523
(1.295 to 1.792)
1.269
(1.107 to 1.455)
1.174
(0.9326 to 1.479)
1.364
(1.133 to 1.642)
2.176
(0.1184 to 39.99)
NA [1] 
(NA to NA)
1.368
(1.044 to 1.792)
1.155
(1.004 to 1.330)
1.245
(0.9538 to 1.625)
1.283
(1.104 to 1.490)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
12.Secondary Outcome
Title Accumulation Ratio (Racc) for Cmax of Pimasertib (MSC1936369B): Day 15
Hide Description Accumulation ratio (Racc) for Cmax, calculated as Day 15 Cmax/Day 1 Cmax.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "N" signifies number of subjects evaluable for this outcome measure and "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg Pimasertib (MSC1936369B) 30mg Pimasertib (MSC1936369B) 60mg Pimasertib (MSC1936369B) 90mg Pimasertib (MSC1936369B) 45mg Twice Daily Pimasertib (MSC1936369B) 60mg Twice Daily TNBC: Pimasertib 60mg Once Daily NSCLC: Pimasertib 60mg Once Daily CRC: Pimasertib 60mg Once Daily MEL: Pimasertib 60mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 9 15 9 3 1 16 17 10 13
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
1.525
(1.002 to 2.322)
1.066
(0.7442 to 1.527)
1.106
(0.7904 to 1.546)
1.308
(0.7537 to 2.268)
1.467
(0.02541 to 84.67)
NA [1] 
(NA to NA)
1.203
(0.9074 to 1.595)
1.059
(0.8875 to 1.263)
1.247
(0.8719 to 1.784)
1.393
(1.091 to 1.780)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
13.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for SAR245409
Hide Description [Not Specified]
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 11 36 3 3 4 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: nanogram per millilitre (ng/mL)
Day 1 (n=6, 11, 36, 3, 3, 4, 26, 23, 18, 15)
192.0
(115.6 to 316.3)
295.7
(189.0 to 462.6)
256.9
(203.5 to 324.3)
224.5
(99.72 to 505.2)
130.2
(20.76 to 816.5)
64.22
(19.25 to 214.2)
323.6
(258.4 to 405.2)
240.6
(164.6 to 351.6)
239.6
(158.8 to 361.4)
212.5
(129.3 to 349.4)
Day 15 (n=6, 6, 25, 1, 1, 3, 17, 17, 10, 13)
199.8
(114.4 to 349.1)
224.1
(132.7 to 378.4)
222.9
(143.7 to 345.7)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
117.2
(7.210 to 1907)
326.0
(256.4 to 414.6)
235.5
(144.6 to 383.3)
178.9
(82.31 to 389.0)
226.6
(143.9 to 356.7)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
14.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of SAR245409
Hide Description The time to reach maximum plasma concentration (Tmax) of SAR245409 was calculated.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 11 36 3 3 4 26 24 18 15
Median (Full Range)
Unit of Measure: hours
Day 1 (n=6, 11, 36, 3, 3, 4, 26, 23, 18, 15)
1.510
(0.53 to 2.08)
1.150
(0.50 to 4.10)
1.500
(0.50 to 23.80)
1.500
(1.00 to 8.00)
2.050
(1.50 to 2.07)
1.540
(0.50 to 4.00)
1.500
(0.52 to 8.03)
2.000
(0.50 to 4.17)
2.000
(0.43 to 8.05)
1.500
(0.95 to 4.00)
Day 15 (n=6, 8, 25, 1, 1, 3, 17, 17, 10, 13)
1.265
(1.00 to 2.00)
1.750
(0.53 to 3.00)
1.970
(1.00 to 8.13)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
1.550
(1.50 to 8.00)
2.030
(0.52 to 7.98)
1.530
(0.92 to 8.00)
1.750
(0.50 to 8.00)
1.050
(0.50 to 3.97)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
15.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Last Sampling Time (0-24 Hours) of SAR245409
Hide Description Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time (0-24 hours) at which the concentration is at or above the lower limit of quantification. Unit of assessment was hour*nanogram per milliliter (hr*ng/mL).
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 11 36 3 3 4 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr*ng/mL
Day 1 (n=6, 11, 36, 3, 3, 4, 26, 23, 18, 15)
683.6
(248.9 to 1878)
1248
(760.1 to 2050)
1566
(1162 to 2111)
3032
(1425 to 6454)
634.0
(111.8 to 3595)
226.2
(82.99 to 616.7)
1976
(1449 to 2693)
1408
(962.5 to 2059)
1479
(824.6 to 2653)
854.9
(505.0 to 1447)
Day 15 (n=6, 8, 25, 1, 1, 3, 17, 17, 10, 13)
861.0
(371.5 to 1995)
1125
(558.3 to 2266)
1334
(895.8 to 1986)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
537.5
(56.10 to 5150)
2232
(1512 to 3297)
1437
(922.1 to 2239)
1365
(543.4 to 3431)
968.8
(554.8 to 1692)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
16.Secondary Outcome
Title Area Under the Concentration-Time Curve (AUC) During a Dosing Interval (Tau) of SAR245409
Hide Description [Not Specified]
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 11 36 3 3 4 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr*ng/mL
Day 1 (n=6, 11, 36, 3, 3, 3, 24, 23, 17, 15)
746.9
(275.5 to 2024)
1265
(784.5 to 2041)
1601
(1195 to 2145)
3032
(1425 to 6454)
634.0
(111.8 to 3595)
298.6
(120.4 to 740.6)
2115
(1535 to 2915)
1480
(1026 to 2137)
1542
(851.5 to 2792)
948.4
(601.8 to 1495)
Day 15 (n=6, 8, 25, 1, 1, 3, 17, 17, 10, 13)
887.9
(397.9 to 1981)
1168
(611.5 to 2232)
1362
(918.9 to 2018)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
537.5
(56.10 to 5150)
2390
(1696 to 3368)
1437
(922.1 to 2239)
1365
(543.4 to 3431)
1074
(636.9 to 1811)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
17.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (0-inf) of SAR245409: Day 1
Hide Description

Area under the concentration-time curve from time 0 extrapolated to infinity, calculated as AUC0-t + last observed concentration (Clast)/terminal rate constant (λz), using the Linear up/Log down method.

Terminal rate constant (λz). The regression analysis (determination of λz) was to contain as many data points as possible (but excluding Cmax) and had to include concentration data from at least 3 different time points, consistent with the assessment of a straight line (the terminal elimination phase) on the log-transformed scale.

Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "N" signifies number of subjects evaluable for this outcome measure and "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 5 9 31 2 1 3 20 17 12 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr*ng/mL
716.5
(181.8 to 2823)
1165
(648.3 to 2093)
1504
(1113 to 2034)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
331.2
(151.5 to 724.1)
1974
(1408 to 2768)
1445
(1019 to 2049)
1261
(579.4 to 2743)
1142
(750.4 to 1739)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
18.Secondary Outcome
Title Apparent Terminal Half-Life (t1/2) of SAR245409
Hide Description [Not Specified]
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 11 36 3 3 4 26 24 18 15
Median (Full Range)
Unit of Measure: hour
Day 1 (n=6, 9, 31, 2, 2, 3, 20, 19, 13, 14)
3.055
(1.78 to 7.57)
3.300
(1.45 to 8.94)
3.390
(0.964 to 9.28)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
3.310
(2.47 to 3.37)
3.755
(1.32 to 7.59)
3.300
(2.54 to 27.9)
4.070
(2.14 to 9.02)
3.120
(1.32 to 6.03)
Day 15 (n=6, 8, 22, 1, 1, 2, 10, 15, 8, 10)
3.700
(2.07 to 5.60)
4.570
(1.81 to 6.49)
4.560
(2.37 to 35.2)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
2.840
(1.48 to 5.63)
4.050
(2.74 to 7.87)
6.170
(3.43 to 11.8)
3.065
(1.79 to 5.37)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
19.Secondary Outcome
Title Total Body Clearance (CL/f) of SAR245409
Hide Description The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the dose with area under the plasma concentration time curve from time zero to infinity (AUC 0-inf)=Dose/AUC 0-inf.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 11 36 2 1 4 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: litre per hour
Day 1 (n=5, 9, 31, 2, 1, 3, 20, 17, 12, 12)
41.80
(10.62 to 164.5)
42.93
(23.89 to 77.16)
46.54
(34.42 to 62.94)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
151.4
(69.37 to 330.4)
35.43
(25.26 to 49.69)
48.40
(34.12 to 68.64)
55.51
(25.52 to 120.7)
61.29
(40.26 to 93.30)
Day 15 (n=6, 8, 25, 1, 1, 3, 17, 17, 10, 13)
33.78
(15.16 to 75.26)
42.81
(22.39 to 81.85)
51.38
(34.68 to 76.13)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
92.90
(9.667 to 892.8)
29.28
(20.78 to 41.26)
48.69
(31.25 to 75.88)
51.24
(20.38 to 128.8)
65.16
(38.64 to 109.9)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
20.Secondary Outcome
Title Apparent Volume of Distribution of Total SAR245409 During the Terminal Phase Following Oral Administration (Vz/f)
Hide Description Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Apparent volume of distribution during the terminal phase, calculated by CL/f/λz. Terminal rate constant (λz). The regression analysis (determination of λz) was to contain as many data points as possible (but excluding Cmax) and had to include concentration data from at least 3 different time points, consistent with the assessment of a straight line (the terminal elimination phase) on the log-transformed scale.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 11 36 2 1 4 26 24 18 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: litre
Day 1 (n=5, 9, 31, 2, 1, 3, 20, 17, 12, 12)
174.8
(71.24 to 429.0)
223.4
(116.2 to 429.6)
238.5
(179.0 to 317.8)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
658.0
(211.9 to 2044)
175.2
(123.9 to 247.9)
251.4
(158.4 to 398.9)
353.6
(177.1 to 705.8)
270.3
(175.6 to 416.0)
Day 15 (n=6, 8, 25, 1, 1, 2, 17, 17, 10, 13 )
165.7
(99.48 to 276.1)
257.2
(156.7 to 422.1)
355.9
(212.5 to 596.2)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
132.8
(96.16 to 183.4)
247.1
(149.4 to 410.7)
475.9
(128.0 to 1769)
293.4
(141.6 to 607.7)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
21.Secondary Outcome
Title Accumulation Ratio (Racc) for AUCtau of SAR245409: Day 15
Hide Description Accumulation ratio (Racc) for AUCtau, calculated as Day 15 dosing interval AUCtau divided by Day 1 dosing interval AUCtau.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set. Here "N" signifies number of participant analyzed for this outcome measure and "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 8 25 1 1 3 15 17 10 13
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
1.189
(0.6118 to 2.311)
1.004
(0.4637 to 2.175)
0.9450
(0.6749 to 1.323)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
1.800
(0.1724 to 18.79)
1.256
(0.9407 to 1.676)
0.9887
(0.7202 to 1.357)
1.187
(0.7614 to 1.850)
1.022
(0.6346 to 1.645)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
22.Secondary Outcome
Title Accumulation Ratio (Racc) for Cmax of SAR245409: Day 15
Hide Description Accumulation ratio (Racc) for Cmax, calculated as Day 15 Cmax divided by Day 1 Cmax.
Time Frame Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
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Hide Analysis Population Description
The PK analysis set. Here "N" signifies number of participant analyzed for this outcome measure and "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title SAR245409 30mg SAR245409 50mg SAR245409 70mg SAR245409 90mg SAR245409 30mg Twice Daily SAR245409 50mg Twice Daily TNBC: SAR245409 70mg Once Daily NSCLC: SAR245409 70mg Once Daily CRC: SAR245409 70mg Once Daily MEL: SAR245409 70mg Once Daily
Hide Arm/Group Description:
SAR245409 capsule administered at a single oral dose of 30 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered twice, orally, at a dose of 50 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
SAR245409 capsule administered at a single oral dose of 70 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 6 8 25 1 1 3 17 17 10 13
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.041
(0.6293 to 1.722)
0.8133
(0.3484 to 1.898)
0.8962
(0.6151 to 1.306)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
1.336
(0.03347 to 53.32)
1.070
(0.8319 to 1.375)
0.8950
(0.6951 to 1.152)
0.9611
(0.6441 to 1.434)
0.9942
(0.5447 to 1.815)
[1]
Data was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.
23.Secondary Outcome
Title pS6 Concentrations in Peripheral Blood Mononuclear Cells (PBMCs)
Hide Description pS6 Concentrations in PBMCs was measured during DDI Evaluation period and Cycle 1 for DE cohorts. DDI evaluation period is a 4-day period that was performed within 1 week prior to Day 1 Cycle 1. In DDI evaluation period, On Day 1, SAR245409 was be administered alone, and on Day 3, Pimasertib was administered alone. No data were planned to be collected for "Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily", "Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily", "Pimasertib (MSC1936369) 30mg and SAR245409 70mg Once Daily" and "Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily" reporting arms.
Time Frame DDI Evaluation: Day 1 and 3 (predose, 2, 4, 8 and 24 hours (hr) postdose); Day 2 and 4 (24 hr postdose); Cycle 1 Day 1 (C1D1) and C1D15 (predose, 2, 4, 8, 24 hr postdose); C1D2 and C1D16 (24 hr postdose); C1D19 (predose, 2 hr postdose)
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Hide Analysis Population Description
The Biomarker Analysis Set for pharmacodynamics (PD) marker analysis in PBMC included all subjects who received at least the first dose of both drugs and had provided at least one pre-dose sample and one post-dose sample. Here "n" signifies the number of subjects evaluable at the specific time points.
Arm/Group Title Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 milligram (mg) along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 90 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Overall Number of Participants Analyzed 1 1 1 1 1 3 1
Mean (Standard Deviation)
Unit of Measure: fluorescence intensity
DDI Day 1: Pre-dose (n= 1, 0, 0, 0, 0, 0, 1) 61.02 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 33.78 [1]   (NA)
DDI Day 1: 2hr post-dose (n= 1,0,0,0,0,0,1) 36.15 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 29.84 [1]   (NA)
DDI Day 1: 4hr post-dose (n= 1,0,0,0,0,0,1) 89.14 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 30.28 [1]   (NA)
DDI Day 1: 8 hr post-dose(n= 1, 0, 0, 0, 0, 0, 1) 54.54 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 44.88 [1]   (NA)
DDI Day 1: 24hr post-dose (n= 1,0,0,0,0,0,0) 88.80 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
DDI Day 2: 24hr post-dose (n= 0,0,0,0,0,0,1) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 28.86 [1]   (NA)
DDI Day 3: Pre-dose (n= 1, 0, 0, 0, 0, 0, 1) 57.51 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 14.90 [1]   (NA)
DDI Day 3: 2hr post-dose (n= 1,0,0,0,0,0,1) 55.93 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 34.06 [1]   (NA)
DDI Day 3: 4hr post-dose (n= 1,0,0,0,0,0,1) 36.76 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 1.03 [1]   (NA)
DDI: Day 3: 8 hr post-dose(n= 1, 0, 0, 0, 0, 0, 1) 1.08 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 40.40 [1]   (NA)
DDI:Day 3: 24hr post-dose (n= 1,0,0,0,0,0,0) 87.60 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
DDI Day 4: 24hr post-dose (n= 0,0,0,0,0,0,1) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 1.04 [1]   (NA)
C1D1: Pre dose (n= 1,1,1,1,1,1,1) 51.32 [1]   (NA) 83.52 [1]   (NA) 96.98 [1]   (NA) 47.09 [1]   (NA) 50.17 [1]   (NA) 4.18 [1]   (NA) 36.03 [1]   (NA)
C1D1: 2hr postdose (n= 1,1,1,1,1,1,1) 31.08 [1]   (NA) 24.48 [1]   (NA) 56.41 [1]   (NA) 23.89 [1]   (NA) 5.72 [1]   (NA) 0.92 [1]   (NA) 1.04 [1]   (NA)
C1D1: 4hr postdose (n= 1,1,1,1,1,1,1) 25.71 [1]   (NA) 46.95 [1]   (NA) 50.11 [1]   (NA) 29.85 [1]   (NA) 18.21 [1]   (NA) 0.72 [1]   (NA) 0.94 [1]   (NA)
C1D1: 8hr postdose (n= 1,1,1,1,1,1,1) 3.02 [1]   (NA) 1.28 [1]   (NA) 84.57 [1]   (NA) 19.75 [1]   (NA) 6.21 [1]   (NA) 1.18 [1]   (NA) 0.96 [1]   (NA)
C1D1: 24hr postdose(n= 1,1,1,1,0,0,0) 46.16 [1]   (NA) 72.14 [1]   (NA) 74.15 [1]   (NA) 53.47 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
C1D2: 24hr postdose (n= 0,0,0,0,1,1,1) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 24.66 [1]   (NA) 1.61 [1]   (NA) 1.00 [1]   (NA)
C1D15: pre-dose (n= 1,1,1,1,1,0,1) 43.48 [1]   (NA) 81.29 [1]   (NA) 67.69 [1]   (NA) 1.20 [1]   (NA) 33.43 [1]   (NA) NA [2]   (NA) 0.98 [1]   (NA)
C1D15: 2hr postdose (n= 1,1,1,1,1,0,1) 26.41 [1]   (NA) 43.70 [1]   (NA) 48.23 [1]   (NA) 15.02 [1]   (NA) 21.11 [1]   (NA) NA [2]   (NA) 1.06 [1]   (NA)
C1D15: 4hr postdose (n= 1,1,1,1,1,0,1) 41.34 [1]   (NA) 53.37 [1]   (NA) 92.67 [1]   (NA) 0.96 [1]   (NA) 19.68 [1]   (NA) NA [2]   (NA) 1.03 [1]   (NA)
C1D15: 8hr postdose (n= 1,1,1,1,1,0,1) 0.53 [1]   (NA) 45.97 [1]   (NA) 77.62 [1]   (NA) 36.06 [1]   (NA) 30.08 [1]   (NA) NA [2]   (NA) 0.88 [1]   (NA)
C1D15: 24hr postdose (n= 1,1,1,1,0,0,0) 69.93 [1]   (NA) 0.76 [1]   (NA) 114.39 [1]   (NA) 70.46 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
C1D16: 24hr postdose (n= 0,0,0,0,1,0,1) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 24.36 [1]   (NA) NA [2]   (NA) 0.98 [1]   (NA)
C1D19: pre-dose (n= 1,1,1,1,1,0,1) 68.48 [1]   (NA) 90.02 [1]   (NA) 125.77 [1]   (NA) 82.06 [1]   (NA) 30.58 [1]   (NA) NA [2]   (NA) 49.62 [1]   (NA)
C1D19: 2hr postdose (n= 1,0,0,0,0,0,0) 4.34 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
[1]
Data for standard deviation was not estimable as only one subject analyzed.
[2]
The parameter was not analyzed at specified time point because there were no subjects for which data was collected at the specified time point.
24.Secondary Outcome
Title pERK Concentrations in PBMCs
Hide Description pERK Concentrations in PBMCs was measured during DDI Evaluation period and Cycle 1 for DE cohorts. DDI evaluation period is a 4-day period that was performed within 1 week prior to Day 1 Cycle 1. In DDI evaluation period, On Day 1, SAR245409 was be administered alone, and on Day 3, Pimasertib was administered alone. No data were planned to be collected for "Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily", "Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily", "Pimasertib (MSC1936369) 30mg and SAR245409 70mg Once Daily" and "Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily" reporting arms.
Time Frame DDI Evaluation: Day 1 and 3 (predose, 2, 4, 8 and 24 hours (hr) postdose); Day 2 and 4 (24 hr postdose); C1D1 and C1D15 (predose, 2, 4, 8, 24 hr postdose); C1D2 and C1D16 (24 hr postdose); C1D19 (predose, 2 hr postdose)
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Hide Analysis Population Description
Biomarker Analysis Set for pharmacodynamics marker analysis in PBMC included all subjects who received at least first dose of both drugs and had provided at least one pre-dose sample and one post-dose sample. Here "N" signifies number of subject analysed for this outcome measure" and "n" signifies number of subject analysed at specific time point.
Arm/Group Title Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 milligram (mg) along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 90 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject.
Overall Number of Participants Analyzed 1 1 1 1 1 3 1
Mean (Standard Deviation)
Unit of Measure: fluorescence intensity
DDI Day 1: Predose (n= 1, 0, 0, 0, 0, 0, 1) 6.77 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 10.55 [1]   (NA)
DDI Day 1: 2 hr post-dose (n=1,0,0,0,0.0,1) 8.74 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 10.17 [1]   (NA)
DDI Day 1: 4 hr post-dose ((n=1,0,0,0,0,0,1) 6.10 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 6.50 [1]   (NA)
DDI Day 1: 8 hr post-dose(n= 1, 0, 0, 0, 0, 0, 1) 7.42 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 9.36 [1]   (NA)
DDI Day 1: 24 hr post-dose (n=1,0,0,0,0,0,0) 10.84 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
DDI Day 2: 24 hr post-dose ((n= 0,0,0,0,0,0,1) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 8.32 [1]   (NA)
DDI Day 3: Pre-dose (n= 1, 0, 0, 0, 0, 0, 1) 9.46 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 8.94 [1]   (NA)
DDI Day 3: 2 hr post-dose (n=1,0,0,0,0,0,1) 3.12 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 15.82 [1]   (NA)
DDI Day 3: 4 hr post-dose (n-1,0,0,0,0,0,1) 6.74 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 0.68 [1]   (NA)
DDI Day 3: 8 hr post-dose(n= 1, 0, 0, 0, 0, 0, 1) 0.81 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 15.68 [1]   (NA)
DDI Day 3: 24 hr post-dose (n=1,0,0,0,0,0,0) 6.18 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
DDI Day 4: 24 hr post-dose (n=0,0,0,0,0,0,1) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 1.06 [1]   (NA)
C1D1: Pre dose (n=1,1,1,1,1,1,1) 5.56 [1]   (NA) 3.45 [1]   (NA) 6.96 [1]   (NA) 3.25 [1]   (NA) 3.35 [1]   (NA) 1.97 [1]   (NA) 7.42 [1]   (NA)
C1D1: 2hr postdose(n= 1,1,1,1,1,1,1) 2.37 [1]   (NA) 1.33 [1]   (NA) 2.78 [1]   (NA) 1.54 [1]   (NA) 1.40 [1]   (NA) 0.95 [1]   (NA) 1.04 [1]   (NA)
C1D1: 4hr postdose(n= 1,1,1,1,1,1,1) 2.85 [1]   (NA) 1.37 [1]   (NA) 2.91 [1]   (NA) 1.24 [1]   (NA) 1.96 [1]   (NA) 1.11 [1]   (NA) 1.01 [1]   (NA)
C1D1: 8hr postdose(n= 1,1,1,1,1,1,1) 0.67 [1]   (NA) 0.94 [1]   (NA) 3.40 [1]   (NA) 1.96 [1]   (NA) 1.27 [1]   (NA) 1.12 [1]   (NA) 0.82 [1]   (NA)
C1D1: 24hr postdose(n= 1,1,1,1,0,0,0) 6.23 [1]   (NA) 2.15 [1]   (NA) 4.59 [1]   (NA) 6.26 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
C1D2: 24hr postdose(n= 0,0,0,0,1,1,1) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 3.45 [1]   (NA) 1.26 [1]   (NA) 1.05 [1]   (NA)
C1D15: pre-dose(n= 1,1,1,1,1,0,1) 3.79 [1]   (NA) 2.26 [1]   (NA) 5.29 [1]   (NA) 1.41 [1]   (NA) 1.93 [1]   (NA) NA [2]   (NA) 2.03 [1]   (NA)
C1D15: 2hr postdose (n= 1,1,1,1,1,0,1) 2.16 [1]   (NA) 1.34 [1]   (NA) 2.83 [1]   (NA) 1.60 [1]   (NA) 1.55 [1]   (NA) NA [2]   (NA) 0.94 [1]   (NA)
C1D15: 4hr postdose (n= 1,1,1,1,1,0,1) 1.87 [1]   (NA) 1.34 [1]   (NA) 2.50 [1]   (NA) 0.94 [1]   (NA) 1.20 [1]   (NA) NA [2]   (NA) 0.81 [1]   (NA)
C1D15: 8hr postdose (n= 1,1,1,1,1,0,1) 1.92 [1]   (NA) 2.08 [1]   (NA) 3.38 [1]   (NA) 1.10 [1]   (NA) 1.74 [1]   (NA) NA [2]   (NA) 0.99 [1]   (NA)
C1D15: 24hr postdose (n= 1,1,1,1,0,0,0) 4.97 [1]   (NA) 0.94 [1]   (NA) 5.33 [1]   (NA) 4.70 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
C1D16: 24hr postdose (n= 0,0,0,0,1,0,1) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 2.36 [1]   (NA) NA [2]   (NA) 0.99 [1]   (NA)
C1D19: pre-dose (n= 1,1,1,1,1,0,1) 6.54 [1]   (NA) 2.61 [1]   (NA) 4.47 [1]   (NA) 5.44 [1]   (NA) 2.07 [1]   (NA) NA [2]   (NA) 5.72 [1]   (NA)
C1D19: 2hr postdose (n= 1,0,0,0,0,0,0) 1.60 [1]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA)
[1]
Data for standard deviation was not estimable as only one subject analyzed.
[2]
The parameter was not analyzed at specified time point because there were no subjects for which data was collected at the specified time point.
25.Secondary Outcome
Title Number of Subjects With Complete Tumor Response (CR), Partial Tumor Response (PR), or Stable Disease (SD)
Hide Description CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD= At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame From the date of randomisation every 6 weeks up to assessed up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Analysis Set (EEF) included all subjects who received at least 1 trial treatment dose (Pimasertib or SAR245409) and had radiographic baseline and at least one evaluable post baseline tumor assessment.
Arm/Group Title Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily Pimasertib (MSC1936369B) 30mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily CRC: Pimasertib 60mg and SAR245409 70mg Once Daily MEL: Pimasertib 60mg and SAR245409 70mg Once Daily
Hide Arm/Group Description:
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 milligram (mg) along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 15 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 30 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 90 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered at a single oral dose of 60 mg along with single oral dose of 90 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 60 mg along with twice oral dose of 30 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Pimasertib (MSC1936369B) capsule was administered twice orally at a dose of 45 mg along with twice oral dose of 50 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
Subjects with relapsed or refractory metastatic triple negative breast cancer (TNBC) defined as estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) negative carcinoma of the breast with no approved therapies in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of each 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Subjects with a histologically confirmed diagnosis of relapsed or refractory metastatic non-small cell lung cancer (NSCLC) in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Subjects with relapsed or refractory metastatic colorectal carcinoma/cancer (CRC) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Subjects with relapsed or refractory metastatic melanoma (MEL) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
Overall Number of Participants Analyzed 3 3 3 4 4 2 13 11 2 1 3 16 20 11 14
Measure Type: Number
Unit of Measure: subjects
Stable disease 3 2 2 3 1 2 4 6 0 1 2 7 10 1 7
Progressive disease 0 0 1 1 1 0 9 3 2 0 1 8 6 9 4
Complete Response 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1
Partial Response 0 1 0 0 0 0 0 2 0 0 0 0 1 0 1
Not Evaluable 0 0 0 0 2 0 0 0 0 0 0 1 3 1 1
Time Frame Baseline up to 30 Days after last dose; assessed up to 4 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title MSC1936369B (Pimasertib) 15mg and SAR245409 30mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 30mg Once Daily MSC1936369B (Pimasertib) 15mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 90mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 90mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 30mg Twice Daily MSC1936369B (Pimasertib) 45mg and SAR245409 50mg Twice Daily TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily CRC: Pimasertib 60mg and SAR245409 70mg Once Daily MEL: Pimasertib 60mg and SAR245409 70mg Once Daily
Hide Arm/Group Description MSC1936369B (Pimasertib) capsule administered at a single dose of 15 milligram (mg) on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 30 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered at a single dose of 30 mg on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 30 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered at a single dose of 15 mg on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 50 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered at a single dose of 30 mg on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 50 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered at a single dose of 60 mg on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 50 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered at a single dose of 30 mg on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 70 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered at a single dose of 60 mg on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 70 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered at a single dose of 90 mg on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 70 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered at a single dose of 60 mg on day 1 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 90 mg on day 1 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered twice at a dose of 60 mg on day 1 and 15 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 30 mg on day 1 and 15 of each cycle (21 days) (DE cohort). MSC1936369B (Pimasertib) capsule administered twice at a dose of 45 mg on day 1 and 15 of each cycle (21 days) along with SAR245409 capsule administered at a single dose of 50 mg on day 1 and 15 of each cycle (21 days) (DE cohort). Participants with relapsed or refractory metastatic triple negative breast cancer (TNBC) defined as estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) negative carcinoma of the breast with no approved therapies received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the participant (DSE Cohort). Participants with a histologically confirmed diagnosis of relapsed or refractory metastatic non-small cell lung cancer (NSCLC) in disease specific expansion (DSE) cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the participant (DSE Cohort). Participants with relapsed or refractory metastatic colorectal carcinoma/cancer (CRC) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the participant (DSE Cohort). Participants with relapsed or refractory metastatic melanoma (MEL) in DSE cohort received Pimasertib (MSC1936369B) capsule at a single oral dose of 60 mg along with single oral dose of 70 mg SAR245409 capsule on Day 1 of 21 days cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the participant (DSE Cohort).
All-Cause Mortality
MSC1936369B (Pimasertib) 15mg and SAR245409 30mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 30mg Once Daily MSC1936369B (Pimasertib) 15mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 90mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 90mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 30mg Twice Daily MSC1936369B (Pimasertib) 45mg and SAR245409 50mg Twice Daily TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily CRC: Pimasertib 60mg and SAR245409 70mg Once Daily MEL: Pimasertib 60mg and SAR245409 70mg Once Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
MSC1936369B (Pimasertib) 15mg and SAR245409 30mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 30mg Once Daily MSC1936369B (Pimasertib) 15mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 50mg Once Daily MSC1936369B (Pimasertib) 30mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 90mg and SAR245409 70mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 90mg Once Daily MSC1936369B (Pimasertib) 60mg and SAR245409 30mg Twice Daily MSC1936369B (Pimasertib) 45mg and SAR245409 50mg Twice Daily TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily CRC: Pimasertib 60mg and SAR245409 70mg Once Daily MEL: Pimasertib 60mg and SAR245409 70mg Once Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      0/3 (0.00%)      2/3 (66.67%)      1/4 (25.00%)      1/4 (25.00%)      1/3 (33.33%)      14/19 (73.68%)      10/14 (71.43%)      1/3 (33.33%)      2/3 (66.67%)      3/4 (75.00%)      16/26 (61.54%)      13/24 (54.17%)      10/18 (55.56%)      8/15 (53.33%)    
Blood and lymphatic system disorders                               
FEBRILE NEUTROPENIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
LEUKOPENIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ANAEMIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0
THROMBOCYTOPENIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
Cardiac disorders                               
ATRIAL FLUTTER * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ATRIAL FIBRILLATION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  2/15 (13.33%) 
BRADYCARDIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
CARDIO-RESPIRATORY ARREST * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
RIGHT VENTRICULAR DYSFUNCTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  1/15 (6.67%) 
Gastrointestinal disorders                               
NAUSEA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  1/14 (7.14%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/26 (0.00%)  1/24 (4.17%)  2/18 (11.11%)  0/15 (0.00%) 
VOMITING * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/26 (0.00%)  0/24 (0.00%)  2/18 (11.11%)  1/15 (6.67%) 
ABDOMINAL PAIN LOWER * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ABDOMINAL PAIN UPPER * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ASCITES * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
DIARRHOEA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/4 (50.00%)  0/26 (0.00%)  0/24 (0.00%)  2/18 (11.11%)  0/15 (0.00%) 
DYSPHAGIA * 1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  1/24 (4.17%)  0/18 (0.00%)  0/15 (0.00%) 
SMALL INTESTINAL OBSTRUCTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ABDOMINAL PAIN * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  1/15 (6.67%) 
INTESTINAL ISCHAEMIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
LARGE INTESTINAL OBSTRUCTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
PANCREATITIS * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
STOMATITIS * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
UPPER GASTROINTESTINAL HAEMORRHAGE * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
General disorders                               
PYREXIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  4/19 (21.05%)  3/14 (21.43%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  2/26 (7.69%)  1/24 (4.17%)  2/18 (11.11%)  0/15 (0.00%) 
DISEASE PROGRESSION * 1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  4/19 (21.05%)  1/14 (7.14%)  0/3 (0.00%)  0/3 (0.00%)  2/4 (50.00%)  1/26 (3.85%)  3/24 (12.50%)  2/18 (11.11%)  0/15 (0.00%) 
GAIT DISTURBANCE * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
FATIGUE * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
FATIGUE * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  2/24 (8.33%)  0/18 (0.00%)  1/15 (6.67%) 
GENERALISED OEDEMA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
Hepatobiliary disorders                               
BILE DUCT OBSTRUCTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
HEPATIC FAILURE * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
HYPERBILIRUBINAEMIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
BILE DUCT STENOSIS * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
Immune system disorders                               
ANAPHYLACTIC REACTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
Infections and infestations                               
CELLULITIS * 1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/18 (0.00%)  1/15 (6.67%) 
FUNGAL SKIN INFECTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
INFLUENZA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
PELVIC ABSCESS * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
LUNG INFECTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/26 (0.00%)  1/24 (4.17%)  0/18 (0.00%)  0/15 (0.00%) 
PNEUMONIA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  3/26 (11.54%)  1/24 (4.17%)  1/18 (5.56%)  1/15 (6.67%) 
SEPSIS * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  3/26 (11.54%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ABDOMINAL INFECTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ESCHERICHIA INFECTION * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  1/15 (6.67%) 
ESCHERICHIA SEPSIS * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
GASTROENTERITIS * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
Injury, poisoning and procedural complications                               
FALL * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
SUBDURAL HAEMATOMA * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ACCIDENTAL OVERDOSE * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
HUMERUS FRACTURE * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)  0/15 (0.00%) 
OVERDOSE * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
Investigations                               
BLOOD CREATININE INCREASED * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/18 (0.00%)  0/15 (0.00%) 
ASPARTATE AMINOTRANSFERASE INCREASED * 1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/18 (5.56%)