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A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01781572
Recruitment Status : Completed
First Posted : February 1, 2013
Results First Posted : August 12, 2020
Last Update Posted : December 7, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Locally Advanced or Metastatic NRAS Mutant Melanoma
Interventions Drug: LEE011
Drug: MEK162
Enrollment 102
Recruitment Details Upon study entry, all patients were required to provide either an archival tumor biopsy with the corresponding pathology report or a newly obtained tumor biopsy. Both parts of the study were limited to patients aged 18 or older with metastatic or locally advanced NRAS-mutant melanoma.
Pre-assignment Details

Screening details:

Screening assessments were performed within 14 days prior to the first dose of ribociclib and binimetinib except for the pretreatment tumor biopsy, which was performed within 28 days before dosing. A total of 23 patients were screened but not enrolled.

Arm/Group Title Phase 1b 28-Day Schedule Phase 1b 21-Day Schedule Phase 2 (Dose-expansion Phase)
Hide Arm/Group Description

A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 28-day schedule was binimetinib 45 mg BID + ribociclib 200 mg QD.

28-Day Schedule: ribociclib was taken QD for 21 consecutive days followed by a 7-day planned break.

Binimetinib was taken BID on a continuous dosing schedule.

A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 21-day schedule was binimetinib 30 mg BID + ribociclib 200 mg QD.

21-Day Schedule: ribociclib QD and binimetinib BID were taken QD for 14 consecutive days followed by a 7-day planned break.

The dose-expansion phase was initiated with a newly recruited group of patients.

A total of 41 patients were treated, and all patients (100%) discontinued treatment. Based on the recommendations of the dose-escalation meetings between the Sponsor and the Investigators, the RP2D and schedule for the combination of binimetinib and ribociclib to be used for the dose-expansion phase of the study was binimetinib 45 mg BID + ribociclib 200 mg QD on the 28-day schedule.

Period Title: MEK162 45mg BID+LEE011 200mg
Started 16 6 41
Completed 0 0 0
Not Completed 16 6 41
Reason Not Completed
Adverse Event             7             0             11
Progressive disease             8             6             23
Withdrawal by Subject             1             0             2
Physician Decision             0             0             4
Death             0             0             1
Period Title: MEK162 45mg BID+LEE011 250mg
Started 3 0 0
Completed 0 0 0
Not Completed 3 0 0
Reason Not Completed
Progressive Disease             2             0             0
Withdrawal by Subject             1             0             0
Period Title: MEK162 30mg BID+LEE011 300mg
Started 4 2 0
Completed 0 0 0
Not Completed 4 2 0
Reason Not Completed
Adverse Event             1             0             0
Progressive Disease             3             2             0
Period Title: MEK162 45mg BID+LEE011 300mg
Started 6 4 0
Completed 0 0 0
Not Completed 6 4 0
Reason Not Completed
Adverse Event             1             1             0
Progressive Disease             4             3             0
Death             1             0             0
Period Title: MEK162 30mg LEE011 200mg
Started 0 5 0
Completed 0 0 0
Not Completed 0 5 0
Reason Not Completed
Progressive Disease             0             5             0
Period Title: MEK162 45mg LEE011 450mg
Started 0 9 0
Completed 0 0 0
Not Completed 0 9 0
Reason Not Completed
Adverse Event             0             1             0
Physician Decision             0             2             0
Progressive Disease             0             6             0
Period Title: MEK162 45mg LEE011 600mg
Started 0 6 0
Completed 0 0 0
Not Completed 0 6 0
Reason Not Completed
Adverse Event             0             1             0
Progressive Disease             0             5             0
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg Phase 2: MEK162 45mg+LEE011 200mg Total
Hide Arm/Group Description MEK162 45mg + LEE011 200mg MEK162 45mg+LEE011 250mg MEK162 30mg+LEE011 300mg MEK162 45mg+LEE011 300mg MEK162 30mg+LEE011 200mg MEK162 45mg+LEE011 200mg MEK162 30mg+LEE011 300mg MEK162 45mg+LEE011 300mg MEK162 45mg+LEE011 450mg MEK162 45mg+LEE011 600mg MEK162 45mg+LEE011 200mg Total of all reporting groups
Overall Number of Baseline Participants 16 3 4 6 5 6 2 4 9 6 41 102
Hide Baseline Analysis Population Description
The baseline analysis population consists of the Full Analysis Set (FAS), which includes all patients who received at least 1 dose of ribociclib or binimetinib.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 3 participants 4 participants 6 participants 5 participants 6 participants 2 participants 4 participants 9 participants 6 participants 41 participants 102 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%
Between 18 and 65 years
9
  56.3%
2
  66.7%
2
  50.0%
4
  66.7%
3
  60.0%
3
  50.0%
1
  50.0%
2
  50.0%
4
  44.4%
5
  83.3%
19
  46.3%
54
  52.9%
>=65 years
7
  43.8%
1
  33.3%
2
  50.0%
2
  33.3%
2
  40.0%
3
  50.0%
1
  50.0%
2
  50.0%
5
  55.6%
1
  16.7%
22
  53.7%
48
  47.1%
Age, Continuous  
Median (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 3 participants 4 participants 6 participants 5 participants 6 participants 2 participants 4 participants 9 participants 6 participants 41 participants 102 participants
62  (14.51) 57  (9.02) 61.5  (21.30) 56  (15.04) 63.0  (7.50) 62.5  (12.687) 55.0  (18.38) 63.5  (19.48) 67.0  (8.59) 58.5  (5.56) 65  (12.35) 61  (12.72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 3 participants 4 participants 6 participants 5 participants 6 participants 2 participants 4 participants 9 participants 6 participants 41 participants 102 participants
Female
8
  50.0%
0
   0.0%
3
  75.0%
1
  16.7%
2
  40.0%
3
  50.0%
1
  50.0%
2
  50.0%
1
  11.1%
5
  83.3%
15
  36.6%
41
  40.2%
Male
8
  50.0%
3
 100.0%
1
  25.0%
5
  83.3%
3
  60.0%
3
  50.0%
1
  50.0%
2
  50.0%
8
  88.9%
1
  16.7%
26
  63.4%
61
  59.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 16 participants 3 participants 4 participants 6 participants 5 participants 6 participants 2 participants 4 participants 9 participants 6 participants 41 participants 102 participants
Caucasian
16
 100.0%
3
 100.0%
4
 100.0%
6
 100.0%
5
 100.0%
6
 100.0%
1
  50.0%
4
 100.0%
9
 100.0%
6
 100.0%
40
  97.6%
100
  98.0%
Other
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  50.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.4%
2
   2.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 16 participants 3 participants 4 participants 6 participants 5 participants 6 participants 2 participants 4 participants 9 participants 6 participants 41 participants 102 participants
82.57  (15.014) 91.47  (20.093) 71.30  (12.631) 97.48  (35.464) 73.66  (8.104) 85.20  (20.733) 80.80  (15.274) 97.20  (24.554) 92.41  (20.709) 62.95  (6.111) 79.63  (17.334) 83.69  (20.621)
Body mass index  
Mean (Standard Deviation)
Unit of measure:  (kg)/m^2
Number Analyzed 16 participants 3 participants 4 participants 6 participants 5 participants 6 participants 2 participants 4 participants 9 participants 6 participants 41 participants 102 participants
28.57  (5.136) 26.84  (5.332) 25.95  (3.347) 30.38  (9.733) 23.85  (2.451) 27.80  (6.185) 27.92  (7.526) 31.71  (5.305) 28.08  (6.594) 23.50  (3.293) 26.69  (5.014) 27.34  (5.841)
ECOG performance status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 3 participants 4 participants 6 participants 5 participants 6 participants 2 participants 4 participants 9 participants 6 participants 41 participants 102 participants
0-Without restriction
10
  62.5%
2
  66.7%
1
  25.0%
2
  33.3%
3
  60.0%
5
  83.3%
2
 100.0%
2
  50.0%
5
  55.6%
5
  83.3%
28
  68.3%
65
  63.7%
1-Restricted in physically strenuous activity
5
  31.3%
0
   0.0%
3
  75.0%
4
  66.7%
2
  40.0%
1
  16.7%
0
   0.0%
2
  50.0%
4
  44.4%
1
  16.7%
13
  31.7%
35
  34.3%
2-Ambulatory and capable of all selfcare
1
   6.3%
1
  33.3%
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%
2
   2.0%
1.Primary Outcome
Title Number of Dose Limiting Toxicities (Phase Ib)
Hide Description To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib.
Time Frame first 28 days of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is comprised of the dose-determining set, which is all patients from the safety set who either met the minimum exposure criterion below and had sufficient safety evaluations during Cycle 1 or discontinued earlier due to DLT during Cycle 1.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 16 3 4 6 5 6 2 4 9 6
Measure Type: Number
Unit of Measure: occurrence
2 0 1 3 0 1 0 1 2 0
2.Primary Outcome
Title Objective Response Rate (ORR) (Phase II)
Hide Description ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1.
Time Frame Approximately 12 months after the FPFV
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise.
Arm/Group Title Phase 2: Dose Expansion
Hide Arm/Group Description:
binimetinib 45 mg BID + ribociclib 200 mg QD (MEK 45mg + LEE 200mg)
Overall Number of Participants Analyzed 41
Measure Type: Count of Participants
Unit of Measure: Participants
8
  19.5%
3.Secondary Outcome
Title Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS) which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 15 3 4 6 4 5 1 4 9 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/ml
2120
(66.2%)
3020
(99.4%)
5280
(27.8%)
3860
(42.3%)
2340
(113%)
2230
(74.5%)
5020 [1] 
(NA%)
2960
(46.4%)
5550
(50.3%)
9840
(65.7%)
[1]
Insufficient number of participants to calculate.
4.Secondary Outcome
Title Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 6 1 1 1 2 3 2 1 2 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/ml
1310
(36.8%)
1070 [1] 
(NA%)
1640 [1] 
(NA%)
1240 [1] 
(NA%)
1610
(76%)
1820
(82.1%)
747
(31.8%)
2740 [1] 
(NA%)
2110
(44.2%)
4060 [1] 
(NA%)
[1]
Insufficient number of participants to calculate.
5.Secondary Outcome
Title Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 13 1 1 2 4 5 2 2 5 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
3080
(63.2%)
15000 [1] 
(NA%)
8650 [1] 
(NA%)
7050
(41.3%)
4700
(28.9%)
4370
(60.3%)
7480
(2.89%)
9570
(50.5%)
11100
(29.1%)
30700
(46.4%)
[1]
Insufficient number of participants to calculate.
6.Secondary Outcome
Title Plasma Concentration-time Profile (AUCtau,ss) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 11 1 0 4 4 4 2 3 4 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
2250
(37.7%)
2450 [1] 
(NA%)
1540
(30.0%)
2180
(12.1%)
2980
(58.9%)
1990
(22.2%)
3680
(40.9%)
2840
(57.5%)
3340
(86.5%)
[1]
Insufficient number of participants to calculate.
7.Secondary Outcome
Title Plasma Concentration-time Profile (Cmin,ss) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 14 2 1 4 4 5 2 2 5 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
88.1
(56.3%)
256
(79.8%)
220 [1] 
(NA%)
113
(56.4%)
117
(39.8%)
97.6
(77.8%)
140
(25.6%)
216
(7.88%)
264
(44.9%)
570
(91.3%)
[1]
Insufficient number of participants to calculate.
8.Secondary Outcome
Title Plasma Concentration-time Profile (Cmin,ss) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 11 2 1 3 4 4 1 3 4 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
73.2
(75.4%)
188
(73.9%)
84.2 [1] 
(NA%)
43.9
(60.7%)
103
(31.4%)
90.4
(20.0%)
123 [1] 
(NA%)
178
(38.1%)
63.9
(94.3%)
179
(98.3%)
[1]
Insufficient number of participants to calculate.
9.Secondary Outcome
Title Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 15 3 4 6 4 5 1 4 9 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
217
(90.5%)
271
(87.4%)
555
(44.4%)
374
(47.9%)
236
(143%)
229
(86.0%)
368 [1] 
(NA%)
307
(33.0%)
506
(65.6%)
1030
(54.1%)
[1]
Insufficient number of participants to calculate.
10.Secondary Outcome
Title Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 15 3 3 6 5 6 2 4 9 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
315
(55.7%)
296
(48.4%)
247
(59.7%)
231
(47.3%)
234
(73.9%)
453
(67.1%)
163
(47.8%)
396
(52.7%)
385
(50.3%)
402
(69.8%)
11.Secondary Outcome
Title Plasma Concentration-time Profile (Cmax,ss) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 14 2 1 4 5 5 2 2 5 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
220
(76.5%)
343
(150%)
220 [1] 
(NA%)
530
(30.6%)
373
(62.4%)
341
(69.0%)
543
(11.9%)
747
(33.0%)
727
(34.7%)
1910
(38.5%)
[1]
Insufficient number of participants to calculate.
12.Secondary Outcome
Title Plasma Concentration-time Profile (Cmax,ss) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 11 2 0 4 5 4 2 3 4 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
441
(52.6%)
309
(1.60%)
284
(14.5%)
376
(18.0%)
444
(36.6%)
367
(31.5%)
590
(12.3%)
452
(59.2%)
471
(75.6%)
13.Secondary Outcome
Title Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 15 3 4 6 4 5 1 4 9 5
Median (Full Range)
Unit of Measure: h
2.12
(1.00 to 24.92)
3.75
(2.12 to 4.10)
2.98
(0.67 to 4.08)
1.50
(0.52 to 4.00)
2.98
(1.98 to 7.95)
1.12
(0.87 to 3.83)
4.22
(4.22 to 4.22)
1.50
(1.00 to 8.00)
2.13
(1.00 to 4.03)
2.03
(1.62 to 2.13)
14.Secondary Outcome
Title Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 15 3 3 6 5 6 2 4 9 5
Median (Full Range)
Unit of Measure: h
1.08
(0.85 to 8.00)
2.05
(0.50 to 2.12)
1.02
(1.00 to 1.97)
2.00
(.52 to 4.00)
1.98
(0.43 to 7.95)
1.11
(0.87 to 2.05)
0.76
(0.52 to 1.00)
2.00
(1.00 to 4.15)
2.17
(1.00 to 8.08)
1.17
(0.47 to 4.02)
15.Secondary Outcome
Title Plasma Concentration-time Profile (Tmax,ss) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 14 2 1 4 5 5 2 2 5 6
Median (Full Range)
Unit of Measure: h
2.25
(0.00 to 7.5)
5.90
(4.00 to 7.80)
23.93
(23.93 to 23.93)
2.99
(2.00 to 4.00)
4.00
(1.03 to 7.87)
1.87
(0.50 to 4.08)
2.03
(1.93 to 2.12)
4.05
(2.08 to 6.02)
3.92
(2.08 to 4.13)
1.93
(1.02 to 4.00)
16.Secondary Outcome
Title Plasma Concentration-time Profile (Tmax,ss) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 11 2 0 4 5 4 2 3 4 6
Median (Full Range)
Unit of Measure: h
1.00
(0.75 to 4.03)
3.03
(1.97 to 4.10)
2.31
(1.00 to 4.00)
1.00
(0.53 to 4.13)
1.96
(1.00 to 3.95)
1.49
(1.05 to 1.93)
2.02
(1.08 to 6.02)
1.92
(0.98 to 2.08)
1.49
(0.00 to 3.63)
17.Secondary Outcome
Title Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 13 1 1 4 4 5 2 2 5 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: (hr*ng/mL) / (hr*ng/mL)
1.51
(53.9%)
2.52 [1] 
(NA%)
2.25 [1] 
(NA%)
2.29
(38.4%)
2.89
(32.8%)
2.28
(54.6%)
3.29
(165%)
3.50
(8.68%)
1.97
(45.4%)
3.95
(58.6%)
[1]
Insufficient number of participants to calculate.
18.Secondary Outcome
Title Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 13 1 1 4 4 5 2 2 5 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: (hr*ng/mL) / (hr*ng/mL
2.53
(45.8%)
7.59 [1] 
(NA%)
1.74 [1] 
(NA%)
3.39
(15.2%)
4.47
(21.5%)
2.26
(27.3%)
3.14
(161%)
3.48
(53.0%)
2.09
(53.5%)
3.06
(26.0%)
[1]
Insufficient number of participants to calculate.
19.Secondary Outcome
Title Plasma Concentration-time Profile (T1/2,ss) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 11 1 1 4 4 5 2 2 4 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
16.7
(83.6%)
32.9 [1] 
(NA%)
28.2 [1] 
(NA%)
28.0
(54.7%)
38.5
(44.4%)
26.9
(82.0%)
275
(64.5%)
49.5
(10.3%)
30.3
(17.6%)
55.3
(73.1%)
[1]
Insufficient number of participants to calculate.
20.Secondary Outcome
Title Plasma Concentration-time Profile (T1/2,ss) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 11 2 0 4 4 4 2 3 4 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
8.17
(30.6%)
7.38
(92.6%)
6.33
(81.1%)
15.0
(54.8%)
5.21
(73.2%)
15.4
(11.4%)
8.95
(23.9%)
8.73
(19.3%)
12.0
(31.2%)
21.Secondary Outcome
Title Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib)
Hide Description To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 8 1 2 5 2 3 0 3 4 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
72.7
(75.4%)
41.2 [1] 
(NA%)
39.2
(26.7%)
67.6
(35.9%)
34.3
(81.7%)
57.2
(52.7%)
93.9
(36.1%)
78.4
(16.0%)
48.7
(68.8%)
[1]
Insufficient number of participants to calculate.
22.Secondary Outcome
Title Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib)
Hide Description To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
Overall Number of Participants Analyzed 6 1 1 1 2 3 2 1 2 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
32.5
(36.3%)
35.9 [1] 
(NA%)
17.8 [1] 
(NA%)
35.5 [1] 
(NA%)
17.9
(80.7%)
23.9
(83.6%)
37.2
(23.0%)
15.9 [1] 
(NA%)
20.8
(45.8%)
10.2 [1] 
(NA%)
[1]
Insufficient number of participants to calculate.
23.Secondary Outcome
Title Number of Participants With Adverse Drug Reactions
Hide Description Safety and tolerability will be characterized through the incidence and severity of adverse drug reactions, serious adverse drug reactions, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, dose reduction and dose intensity.
Time Frame Approximately 12 months after FPFV
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis group consists of the safety set, which included all patients who received at least 1 dose of ribociclib or binimetinib and had at least 1 postbaseline safety assessment.
Arm/Group Title Phase 1b 28-Day MEK162 45mg + LEE011 200mg Phase 1b 28-Day MEK162 45mg+LEE011 250mg Phase 1b 28-Day MEK162 30mg+LEE011 300mg Phase 1b 28-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 30mg+LEE011 200mg Phase 1b 21-Day MEK162 45mg+LEE011 200mg Phase 1b 21-Day MEK162 30mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 300mg Phase 1b 21-Day MEK162 45mg+LEE011 450mg Phase 1b 21-Day MEK162 45mg+LEE011 600mg Phase 2: MEK162 45mg+LEE011 200mg
Hide Arm/Group Description:
MEK162 45mg + LEE011 200mg
MEK162 45mg+LEE011 250mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 30mg+LEE011 200mg
MEK162 45mg+LEE011 200mg
MEK162 30mg+LEE011 300mg
MEK162 45mg+LEE011 300mg
MEK162 45mg+LEE011 450mg
MEK162 45mg+LEE011 600mg
MEK162 45mg+LEE011 200mg
Overall Number of Participants Analyzed 16 3 4 6 5 6 2 4 9 6 41
Measure Type: Count of Participants
Unit of Measure: Participants
16
 100.0%
3
 100.0%
4
 100.0%
6
 100.0%
5
 100.0%
6
 100.0%
2
 100.0%
4
 100.0%
9
 100.0%
6
 100.0%
41
 100.0%
24.Secondary Outcome
Title Duration of Response (DoR) - Phase 2
Hide Description

To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.

Please note: As clinicaltrials.gov only allows numerical data entry, the value of 999 indicates "not estimable" for confidence interval.

Time Frame Approximately 12 months after the FPFV
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise.
Arm/Group Title Phase 2: Dose Expansion
Hide Arm/Group Description:

The dose-expansion phase was initiated with a newly recruited group of patients.

Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule

Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
10.3
(4.1 to 999)
25.Secondary Outcome
Title Time to Progression (TTP) - Phase 2
Hide Description To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Time Frame Approximately 12 months after the FPFV
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise.
Arm/Group Title Phase 2: Dose Expansion
Hide Arm/Group Description:

The dose-expansion phase was initiated with a newly recruited group of patients.

Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule

Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(3.5 to 5.6)
26.Secondary Outcome
Title Progression Free Survival (PFS) - Phase 1b and Phase 2
Hide Description

To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.

In the Phase 1b part, patients were combined for purposes of PFS analyses based on schedule received, since too few patients received any individual dose level to allow for valid PFS estimates within the respective dose levels. This is how the data were analyses and presented for the clinical study report.

Time Frame Approximately 12 months after the FPFV
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise.
Arm/Group Title Phase 1b 28-Day Schedule Phase 1b 21-Day Schedule Phase 2 (Dose-expansion Phase)
Hide Arm/Group Description:

A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 28-day schedule was binimetinib 45 mg BID + ribociclib 200 mg QD.

28-Day Schedule: ribociclib was taken QD for 21 consecutive days followed by a 7-day planned break.

Binimetinib was taken BID on a continuous dosing schedule.

A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 21-day schedule was binimetinib 30 mg BID + ribociclib 200 mg QD.

21-Day Schedule: ribociclib QD and binimetinib BID were taken QD for 14 consecutive days followed by a 7-day planned break.

The dose-expansion phase was initiated with a newly recruited group of patients.

A total of 41 patients were treated, and all patients (100%) discontinued treatment. Based on the recommendations of the dose-escalation meetings between the Sponsor and the Investigators, the RP2D and schedule for the combination of binimetinib and ribociclib to be used for the dose-expansion phase of the study was binimetinib 45 mg BID + ribociclib 200 mg QD on the 28-day schedule.

Overall Number of Participants Analyzed 29 32 41
Median (95% Confidence Interval)
Unit of Measure: months
6.7
(3.5 to 9.2)
4.1
(2.8 to 6.1)
3.7
(3.5 to 5.6)
27.Secondary Outcome
Title Overall Survival (OS) - Phase ll
Hide Description To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Time Frame Approximately 12 months after the FPFV
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise.
Arm/Group Title Phase 2: Dose Expansion
Hide Arm/Group Description:

The dose-expansion phase was initiated with a newly recruited group of patients.

Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule

Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
11.3
(9.3 to 14.2)
28.Secondary Outcome
Title Best Overall Response (BOR) - Phase II
Hide Description To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Time Frame Approximately 12 months after the FPFV
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise.
Arm/Group Title Phase 2: Dose Expansion
Hide Arm/Group Description:

The dose-expansion phase was initiated with a newly recruited group of patients.

Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule

Overall Number of Participants Analyzed 41
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
Partial Response
8
  19.5%
Stable Disease
21
  51.2%
Progressive Disease
6
  14.6%
Non-CR/Non-PD
0
   0.0%
Unknown
6
  14.6%
Time Frame Adverse Events (AE) were collected during the study, which began in June 2013 and concluded February 2018. After signing of the informed consent until 30 days after study treatment discontinuation.
Adverse Event Reporting Description An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
 
Arm/Group Title Phase 1b - 28 Day MEK162 45mg+LEE011 200mg Phase 1b - 28 Day MEK162 45mg+LEE011 250mg Phase 1b - 28 Day MEK162 30mg+LEE011 300mg Phase 1b - 28 Day MEK162 45mg+LEE011 300mg Phase 1b - 21 Day MEK162 30mg+LEE011 200mg Phase 1b - 21 Day MEK162 45mg+LEE011 200mg Phase 1b - 21 Day MEK162 30mg+LEE011 300mg Phase 1b - 21 Day MEK162 45mg+LEE011 300mg Phase 1b - 21 Day MEK162 45mg+LEE011 450mg Phase 1b - 21 Day MEK162 45mg+LEE011 600mg Phase 2 - Dose Expansion Phase
Hide Arm/Group Description MEK162 45mg BID+LEE011 200mg QD MEK162 45mg BID+LEE011 250mg QD MEK162 30mg BID+LEE011 300mg QD MEK162 45mg BID+LEE011 300mg QD MEK162 30mg BID+LEE011 200mg QD MEK162 45mg BID+LEE011 200mg QD MEK162 30mg BID+LEE011 300mg QD MEK162 45mg BID+LEE011 300mg QD MEK162 45mg BID+LEE011 450mg QD MEK162 45mg BID+LEE011 600mg QD

The dose-expansion phase was initiated with a newly recruited group of patients.

Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule

All-Cause Mortality
Phase 1b - 28 Day MEK162 45mg+LEE011 200mg Phase 1b - 28 Day MEK162 45mg+LEE011 250mg Phase 1b - 28 Day MEK162 30mg+LEE011 300mg Phase 1b - 28 Day MEK162 45mg+LEE011 300mg Phase 1b - 21 Day MEK162 30mg+LEE011 200mg Phase 1b - 21 Day MEK162 45mg+LEE011 200mg Phase 1b - 21 Day MEK162 30mg+LEE011 300mg Phase 1b - 21 Day MEK162 45mg+LEE011 300mg Phase 1b - 21 Day MEK162 45mg+LEE011 450mg Phase 1b - 21 Day MEK162 45mg+LEE011 600mg Phase 2 - Dose Expansion Phase
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   3/16 (18.75%)   0/3 (0.00%)   1/4 (25.00%)   1/6 (16.67%)   0/5 (0.00%)   1/6 (16.67%)   0/2 (0.00%)   0/4 (0.00%)   0/9 (0.00%)   1/6 (16.67%)   23/41 (56.10%) 
Hide Serious Adverse Events
Phase 1b - 28 Day MEK162 45mg+LEE011 200mg Phase 1b - 28 Day MEK162 45mg+LEE011 250mg Phase 1b - 28 Day MEK162 30mg+LEE011 300mg Phase 1b - 28 Day MEK162 45mg+LEE011 300mg Phase 1b - 21 Day MEK162 30mg+LEE011 200mg Phase 1b - 21 Day MEK162 45mg+LEE011 200mg Phase 1b - 21 Day MEK162 30mg+LEE011 300mg Phase 1b - 21 Day MEK162 45mg+LEE011 300mg Phase 1b - 21 Day MEK162 45mg+LEE011 450mg Phase 1b - 21 Day MEK162 45mg+LEE011 600mg Phase 2 - Dose Expansion Phase
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   8/16 (50.00%)   2/3 (66.67%)   2/4 (50.00%)   4/6 (66.67%)   2/5 (40.00%)   3/6 (50.00%)   1/2 (50.00%)   3/4 (75.00%)   3/9 (33.33%)   2/6 (33.33%)   22/41 (53.66%) 
Blood and lymphatic system disorders                       
Febrile neutropenia * 1  0/16 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Anaemia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Cardiac disorders                       
Cardio-respiratory arrest * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Atrial fibrillation * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Eye disorders                       
Retinal detachment * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Gastrointestinal disorders                       
Small intestinal * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Nausea * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  1/41 (2.44%) 
Vomiting * 1  1/16 (6.25%)  1/3 (33.33%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  2/41 (4.88%) 
Constipation * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Rectal haemorrhage * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Rectal obstruction * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Intestinal haemorrhage * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Subileus * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Colitis * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Large intestine perforation * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Chills * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Gastrointestinal haemorrhage * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
General disorders                       
Pain * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Fatigue * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Face oedema * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Hepatobiliary disorders                       
Hepatitis * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/41 (0.00%) 
Cholangitis * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Infections and infestations                       
Gastroenteritis * 1  0/16 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Sepsis * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Peritonitis * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Pneumonia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/6 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Upper respiratory tract infection * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Cellulitis * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/6 (33.33%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  2/41 (4.88%) 
Lung infection * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/41 (0.00%) 
Staphylococcal bacteraemia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Erysipelas * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  2/41 (4.88%) 
Bacteraemia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Infection * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Herpes zoster * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Investigations                       
Blood creatine phosphokinase * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Neutrophil * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/41 (0.00%) 
Aspartate aminotransferase increased * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/41 (0.00%) 
Metabolism and nutrition disorders                       
Hypervolaemia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Diabetes mellitus * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Hypokalaemia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Musculoskeletal and connective tissue disorders                       
Muscular weakness * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                       
Tumour haemorrhage * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/5 (40.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Intracranial tumour haemorrhage * 1  0/16 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  4/41 (9.76%) 
Tumour pain * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Nervous system disorders                       
Pyrexia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  2/4 (50.00%)  1/9 (11.11%)  1/6 (16.67%)  4/41 (9.76%) 
Slow speech * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Hemiparesis * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Dizziness * 1  0/16 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Haemorrhage intracranial * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Syncope * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Hemiplegia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Seizure * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/41 (0.00%) 
Renal and urinary disorders                       
Micturition frequency * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Acute kidney injury * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Renal failure * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Haematuria * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Respiratory, thoracic and mediastinal disorders                       
Pulmonary embolism * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Chronic obstructive pulmonary * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Obstructive airways * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/41 (0.00%) 
Pleural effusion * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Skin and subcutaneous tissue disorders                       
Rash maculo-papular * 1  0/16 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Drug eruption * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Vascular disorders                       
Hypotension * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Embolism * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
1
Term from vocabulary, MedDRA Version 19.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1b - 28 Day MEK162 45mg+LEE011 200mg Phase 1b - 28 Day MEK162 45mg+LEE011 250mg Phase 1b - 28 Day MEK162 30mg+LEE011 300mg Phase 1b - 28 Day MEK162 45mg+LEE011 300mg Phase 1b - 21 Day MEK162 30mg+LEE011 200mg Phase 1b - 21 Day MEK162 45mg+LEE011 200mg Phase 1b - 21 Day MEK162 30mg+LEE011 300mg Phase 1b - 21 Day MEK162 45mg+LEE011 300mg Phase 1b - 21 Day MEK162 45mg+LEE011 450mg Phase 1b - 21 Day MEK162 45mg+LEE011 600mg Phase 2 - Dose Expansion Phase
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   16/16 (100.00%)   3/3 (100.00%)   4/4 (100.00%)   6/6 (100.00%)   5/5 (100.00%)   6/6 (100.00%)   2/2 (100.00%)   4/4 (100.00%)   9/9 (100.00%)   6/6 (100.00%)   41/41 (100.00%) 
Blood and lymphatic system disorders                       
Aeaemia * 1  5/16 (31.25%)  2/3 (66.67%)  2/4 (50.00%)  4/6 (66.67%)  2/5 (40.00%)  1/6 (16.67%)  0/2 (0.00%)  1/4 (25.00%)  4/9 (44.44%)  0/6 (0.00%)  10/41 (24.39%) 
Neutropenia * 1  3/16 (18.75%)  1/3 (33.33%)  2/4 (50.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  4/9 (44.44%)  3/6 (50.00%)  5/41 (12.20%) 
Leukopenia * 1  4/16 (25.00%)  0/3 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  1/9 (11.11%)  2/6 (33.33%)  1/41 (2.44%) 
Thrombocytopenia * 1  2/16 (12.50%)  1/3 (33.33%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  1/4 (25.00%)  3/9 (33.33%)  1/6 (16.67%)  3/41 (7.32%) 
Lymphopenia * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  1/4 (25.00%)  2/9 (22.22%)  2/6 (33.33%)  1/41 (2.44%) 
Febrile neutropenia * 1  0/16 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Granulocytopenia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Cardiac disorders                       
Angina pectoris * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Cardiac failure * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Cardio-respiratiory arrest * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Eye disorders                       
Chorioretinopathy * 1  3/16 (18.75%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/9 (11.11%)  2/6 (33.33%)  0/41 (0.00%) 
Retinal detachment * 1  3/16 (18.75%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  2/6 (33.33%)  6/41 (14.63%) 
Vision blurred * 1  2/16 (12.50%)  0/3 (0.00%)  2/4 (50.00%)  0/6 (0.00%)  0/5 (0.00%)  3/6 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/41 (0.00%) 
Retinopathy * 1  2/16 (12.50%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  1/9 (11.11%)  1/6 (16.67%)  0/41 (0.00%) 
Macular oedema * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  2/9 (22.22%)  1/6 (16.67%)  5/41 (12.20%) 
Subretinal fluid * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  1/2 (50.00%)  1/4 (25.00%)  0/9 (0.00%)  2/6 (33.33%)  5/41 (12.20%) 
Dry eye * 1  2/16 (12.50%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Cataract * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Detachment of retinal pigment epithelium * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/41 (0.00%) 
Chorioretinal disorder * 1  1/16 (6.25%)  0/3 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Periorbital oedema * 1  1/16 (6.25%)  0/3 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Retinal disorder * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/41 (0.00%) 
Gastrointestinal disorders                       
Nausea * 1  6/16 (37.50%)  2/3 (66.67%)  3/4 (75.00%)  4/6 (66.67%)  4/5 (80.00%)  3/6 (50.00%)  2/2 (100.00%)  1/4 (25.00%)  1/9 (11.11%)  1/6 (16.67%)  22/41 (53.66%) 
Diarrhoea * 1  6/16 (37.50%)  2/3 (66.67%)  2/4 (50.00%)  4/6 (66.67%)  3/5 (60.00%)  4/6 (66.67%)  2/2 (100.00%)  2/4 (50.00%)  3/9 (33.33%)  5/6 (83.33%)  21/41 (51.22%) 
Vomiting * 1  4/16 (25.00%)  3/3 (100.00%)  4/4 (100.00%)  3/6 (50.00%)  3/5 (60.00%)  2/6 (33.33%)  1/2 (50.00%)  1/4 (25.00%)  2/9 (22.22%)  2/6 (33.33%)  14/41 (34.15%) 
Constipation * 1  3/16 (18.75%)  1/3 (33.33%)  2/4 (50.00%)  3/6 (50.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  1/4 (25.00%)  3/9 (33.33%)  0/6 (0.00%)  8/41 (19.51%) 
Abdominal pain * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  2/2 (100.00%)  1/4 (25.00%)  1/9 (11.11%)  2/6 (33.33%)  5/41 (12.20%) 
Dry mouth * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  2/6 (33.33%)  1/2 (50.00%)  1/4 (25.00%)  3/9 (33.33%)  0/6 (0.00%)  4/41 (9.76%) 
Stomatitis * 1  4/16 (25.00%)  0/3 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  4/41 (9.76%) 
Gastroesophageal reflux disease * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/9 (0.00%)  0/6 (0.00%)  3/41 (7.32%) 
Dyspepsia * 1  2/16 (12.50%)  0/3 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  2/5 (40.00%)  2/6 (33.33%)  0/2 (0.00%)  1/4 (25.00%)  1/9 (11.11%)  0/6 (0.00%)  0/41 (0.00%) 
Abdominal distension * 1  2/16 (12.50%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/41 (2.44%) 
Abdominal pain upper * 1  1/16 (6.25%)  0/3 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Gastritis * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Gingival pain * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
Glossodynia * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/41 (0.00%) 
General disorders                       
Oedema peripheral * 1  7/16 (43.75%)  2/3 (66.67%)  2/4 (50.00%)  3/6 (50.00%)  1/5 (20.00%)  2/6 (33.33%)  0/2 (0.00%)  2/4 (50.00%)  2/9 (22.22%)  0/6 (0.00%)  18/41 (43.90%) 
Fatigue * 1  6/16 (37.50%)  1/3 (33.33%)  3/4 (75.00%)  0/6 (0.00%)  3/5 (60.00%)  5/6 (83.33%)  2/2 (100.00%)  1/4 (25.00%)  3/9 (33.33%)  2/6 (33.33%)  15/41 (36.59%) 
Pyrexia * 1  2/16 (12.50%)  2/3 (66.67%)  1/4 (25.00%)  0/6 (0.00%)  2/5 (40.00%)  1/6 (16.67%)  0/2 (0.00%)  2/4 (50.00%)  2/9 (22.22%)  2/6 (33.33%)  11/41 (26.83%) 
Chills * 1  0/16 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/6 (0.00%)  2/5 (40.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/9 (11.11%)  1/6 (16.67%)  6/41 (14.63%) 
Face oedema * 1  3/16 (18.75%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  1/9 (11.11%)  0/6 (0.00%)  1/41 (2.44%) 
Pain * 1  1/16 (6.25%)  0/3 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/41 (0.00%) 
Astenia * 1  0/16 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  3/41 (7.32%) 
1
Term from vocabulary, MedDRA Version 19.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of the sponsor's agreements with its investigators may vary. However, the sponsor does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e., data from all sites) in the clinical trials.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Pfizer
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01781572    
Other Study ID Numbers: CMEK162X2114
C4211005 ( Other Identifier: Pfizer )
First Submitted: January 24, 2013
First Posted: February 1, 2013
Results First Submitted: May 6, 2020
Results First Posted: August 12, 2020
Last Update Posted: December 7, 2020