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A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab

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: NCT01975831
Recruitment Status : Completed
First Posted : November 5, 2013
Results First Posted : June 22, 2020
Last Update Posted : July 15, 2021
Sponsor:
Collaborators:
MedImmune LLC
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Breast Cancer
Ovarian Cancer
Colorectal Cancer
Cervical Cancer
Renal Cell Carcinoma
Interventions Drug: Durvalumab
Drug: Tremelimumab
Enrollment 104
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
Hide Arm/Group Description

Subjects received durvalumab (0.3 mg/kg every 2 weeks [Q2W] for 13 cycles) and tremelimumab (3 mg/kg every 4 weeks [Q4W] for 6 cycles, then every 12 weeks [Q12W]). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as intravenous (IV) infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Period Title: Overall Study
Started 3 11 4 4 19 16 16 16 15
Completed 0 2 0 0 1 2 0 1 3
Not Completed 3 9 4 4 18 14 16 15 12
Reason Not Completed
Adverse Event             1             2             2             0             1             1             3             4             1
Death             1             1             0             0             1             0             1             0             0
Progressive Disease             1             3             2             4             13             9             10             8             10
Withdrawal by Subject             0             3             0             0             3             1             1             0             0
Physician Decision             0             0             0             0             0             1             0             1             0
Initiation of Subsequent Therapy             0             0             0             0             0             1             0             2             0
Entered Hospice             0             0             0             0             0             1             0             0             0
Unable to Treat Within Protocol Windows             0             0             0             0             0             0             1             0             1
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer Total
Hide Arm/Group Description

Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

 Total of all reporting groups
Overall Number of Baseline Participants 3 11 4 4 19 16 16 16 15 104
Hide Baseline Analysis Population Description
The population comprises all subjects who received any dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 11 participants 4 participants 4 participants 19 participants 16 participants 16 participants 16 participants 15 participants 104 participants
61.3  (7.51) 54.9  (11.93) 50.3  (10.21) 52.8  (11.35) 59.7  (10.91) 49.7  (9.79) 55.4  (14.31) 59.7  (9.71) 53.0  (11.46) 55.5  (11.51)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 11 participants 4 participants 4 participants 19 participants 16 participants 16 participants 16 participants 15 participants 104 participants
Female
3
 100.0%
6
  54.5%
3
  75.0%
3
  75.0%
19
 100.0%
9
  56.3%
16
 100.0%
2
  12.5%
15
 100.0%
76
  73.1%
Male
0
   0.0%
5
  45.5%
1
  25.0%
1
  25.0%
0
   0.0%
7
  43.8%
0
   0.0%
14
  87.5%
0
   0.0%
28
  26.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 11 participants 4 participants 4 participants 19 participants 16 participants 16 participants 16 participants 15 participants 104 participants
Hispanic or Latino
0
   0.0%
1
   9.1%
1
  25.0%
0
   0.0%
1
   5.3%
1
   6.3%
1
   6.3%
0
   0.0%
0
   0.0%
5
   4.8%
Not Hispanic or Latino
3
 100.0%
10
  90.9%
3
  75.0%
4
 100.0%
17
  89.5%
14
  87.5%
14
  87.5%
16
 100.0%
12
  80.0%
93
  89.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
1
   6.3%
1
   6.3%
0
   0.0%
3
  20.0%
6
   5.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 11 participants 4 participants 4 participants 19 participants 16 participants 16 participants 16 participants 15 participants 104 participants
American Indian or Alaska Native
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%
Asian
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
1
   5.3%
2
  12.5%
0
   0.0%
1
   6.3%
3
  20.0%
8
   7.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
0
   0.0%
2
  12.5%
0
   0.0%
2
  13.3%
5
   4.8%
White
3
 100.0%
10
  90.9%
2
  50.0%
4
 100.0%
16
  84.2%
12
  75.0%
12
  75.0%
15
  93.8%
9
  60.0%
83
  79.8%
More than one race
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%
Unknown or Not Reported
0
   0.0%
1
   9.1%
1
  25.0%
0
   0.0%
0
   0.0%
2
  12.5%
2
  12.5%
0
   0.0%
1
   6.7%
7
   6.7%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 11 participants 4 participants 4 participants 19 participants 16 participants 16 participants 16 participants 15 participants 104 participants
ECOG PS 0
2
  66.7%
2
  18.2%
2
  50.0%
1
  25.0%
7
  36.8%
9
  56.3%
6
  37.5%
14
  87.5%
9
  60.0%
52
  50.0%
ECOG PS 1
1
  33.3%
9
  81.8%
2
  50.0%
2
  50.0%
11
  57.9%
7
  43.8%
10
  62.5%
2
  12.5%
6
  40.0%
50
  48.1%
ECOG PS 2
0
   0.0%
0
   0.0%
0
   0.0%
1
  25.0%
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   1.9%
[1]
Measure Description: PS 0 = Fully active, able to carry on all pre-disease performance without restriction; PS 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; PS 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; PS 3 = Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours; PS 4 = Completely disabled; cannot carry on any selfcare; totally confined to bed or chair; PS 5 = Dead
1.Primary Outcome
Title Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Hide Description Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, electrocardiograms, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of study treatment. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population comprises all subjects who received any dose of study treatment.
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
Hide Arm/Group Description:

Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Overall Number of Participants Analyzed 3 11 4 4 19 16 16 16 15
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
3
 100.0%
11
 100.0%
4
 100.0%
4
 100.0%
19
 100.0%
16
 100.0%
16
 100.0%
16
 100.0%
15
 100.0%
Serious TEAE
2
  66.7%
5
  45.5%
4
 100.0%
1
  25.0%
9
  47.4%
8
  50.0%
8
  50.0%
6
  37.5%
8
  53.3%
TEAE leading to treatment discontinuation
1
  33.3%
4
  36.4%
2
  50.0%
0
   0.0%
4
  21.1%
1
   6.3%
4
  25.0%
4
  25.0%
2
  13.3%
2.Secondary Outcome
Title Number of Subjects With Best Overall Immune-related Tumor Response
Hide Description Immune-related tumor response was evaluated by computed tomography at Baseline and every 4 to 8 or 12 weeks on study. Tumor response was designated according to the immune-related Response Criteria (irRC) (Wolchok et al 2009) into the following categories: immune-related complete response (irCR) requires disappearance of all lesions in two consecutive observations not less than 4 weeks apart; immune-related partial response (irPR) requires ≥ 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; immune-related stable disease (irSD) is assigned when neither a 50% decrease from baseline tumor burden nor a 25% increase in tumor burden from nadir can be established; immune-related progressive disease (irPD) requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart.
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
Hide Arm/Group Description:

Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Overall Number of Participants Analyzed 3 10 3 4 18 15 16 15 15
Measure Type: Count of Participants
Unit of Measure: Participants
irCR
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
1
   6.7%
irPR
0
   0.0%
2
  20.0%
0
   0.0%
0
   0.0%
1
   5.6%
1
   6.7%
1
   6.3%
2
  13.3%
3
  20.0%
irSD
2
  66.7%
3
  30.0%
1
  33.3%
0
   0.0%
7
  38.9%
1
   6.7%
2
  12.5%
11
  73.3%
3
  20.0%
irPD
1
  33.3%
5
  50.0%
2
  66.7%
4
 100.0%
10
  55.6%
12
  80.0%
12
  75.0%
2
  13.3%
7
  46.7%
Not evaluable
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.3%
0
   0.0%
1
   6.7%
3.Secondary Outcome
Title Number of Subjects With Best Overall Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Hide Description Tumor response was evaluated using computed tomography and categorized according to RECIST (version 1.1) at Baseline and every 4 to 8 or 12 weeks on study. Per RECIST 1.1 (Eisenhauer et al 2009), target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
Hide Arm/Group Description:

Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Overall Number of Participants Analyzed 3 10 3 4 18 15 16 15 15
Measure Type: Count of Participants
Unit of Measure: Participants
CR
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
1
   6.7%
PR
0
   0.0%
2
  20.0%
0
   0.0%
0
   0.0%
1
   5.6%
1
   6.7%
1
   6.3%
3
  20.0%
3
  20.0%
SD
2
  66.7%
3
  30.0%
1
  33.3%
0
   0.0%
6
  33.3%
1
   6.7%
4
  25.0%
7
  46.7%
3
  20.0%
PD
1
  33.3%
5
  50.0%
2
  66.7%
4
 100.0%
11
  61.1%
12
  80.0%
11
  68.8%
5
  33.3%
8
  53.3%
4.Secondary Outcome
Title Median Progression-free Survival Per irRC Based on Kaplan-Meier Product Limit Estimates
Hide Description PFS was measured from the date of the first dose of study treatment to the date of the first confirmed progression (including clinical progression) or the date of death if a subject died before progression. Per irRC, irPD requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart (Wolchok et al 2009). Subjects who did not experience a PFS event (progression or death) were censored at the date of the last tumor assessment. Subjects with no relevant tumor response assessment were censored at the start date of study treatment.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
Hide Arm/Group Description:

Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Overall Number of Participants Analyzed 3 10 3 4 18 15 16 15 15
Median (Full Range)
Unit of Measure: days
82
(48 to 82)
76
(34 to 1007)
51
(49 to 401)
42
(40 to 52)
54
(12 to 618)
57
(32 to 559)
57
(27 to 223)
326
(54 to 611)
79
(32 to 617)
5.Secondary Outcome
Title Median Progression-free Survival Per RECIST 1.1 Based on Kaplan-Meier Product Limit Estimates
Hide Description PFS was measured from the date of the first dose of study treatment to the date of the first confirmed progression (including clinical progression) or the date of death if a subject died before progression. Per RECIST 1.1, PD requires a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009). Subjects who did not experience a PFS event (progression or death) were censored at the date of the last tumor assessment. Subjects with no relevant tumor response assessment were censored at the start date of study treatment.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
Hide Arm/Group Description:

Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Overall Number of Participants Analyzed 3 10 3 4 18 15 16 15 15
Median (Full Range)
Unit of Measure: days
82
(48 to 251)
76
(34 to 1007)
51
(49 to 401)
42
(40 to 52)
54
(12 to 618)
57
(32 to 559)
56
(27 to 223)
279
(50 to 555)
58
(27 to 617)
6.Secondary Outcome
Title Median Overall Survival (OS) Based on Kaplan-Meier Product Limit Estimates
Hide Description All subjects were monitored for survival follow-up at least every 6 months after study completion for up to 3 years after initiation of treatment. Subjects who continued into the Extension part of the study may have been followed for longer than 3 years if they were still receiving treatment. OS was measured from the date of the first dose of study treatment until the recorded date of death. Subjects without a recorded outcome of death were censored at the date of last contact.
Time Frame Up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
Hide Arm/Group Description:

Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Overall Number of Participants Analyzed 3 10 3 4 18 15 16 15 15
Median (Full Range)
Unit of Measure: days
321
(48 to 482)
592
(44 to 1380)
664
(76 to 1000)
223
(120 to 873)
460
(12 to 652)
267
(56 to 559)
267
(35 to 589)
462
(312 to 611)
583
(32 to 617)
Time Frame Adverse events (AEs) were documented from informed consent through 90 days after the last study drug dose (regardless of causality to study drug), i.e., during the treatment period, which was up to 15 months for those participating in the Core Study and up to 36 months for those continuing in the Extension. All-cause mortality was collected as a part of survival follow-up for up to 3 years after initiation of treatment, or longer (i.e., up to 48 months) for patients continuing in the Extension.
Adverse Event Reporting Description AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.03), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, preferred terms were counted only once per subject at the maximum reported grade.
 
Arm/Group Title Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
Hide Arm/Group Description

Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.

Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.

Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
All-Cause Mortality
Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
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   3/3 (100.00%)   6/11 (54.55%)   4/4 (100.00%)   3/4 (75.00%)   10/19 (52.63%)   11/16 (68.75%)   9/16 (56.25%)   4/16 (25.00%)   7/15 (46.67%) 
Hide Serious Adverse Events
Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
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   2/3 (66.67%)   5/11 (45.45%)   4/4 (100.00%)   1/4 (25.00%)   9/19 (47.37%)   8/16 (50.00%)   8/16 (50.00%)   6/16 (37.50%)   8/15 (53.33%) 
Blood and lymphatic system disorders                   
Anaemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Cardiac disorders                   
Cardiac disorder † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Pericardial effusion † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Sinus tachycardia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Endocrine disorders                   
Hypothalamo-pituitary disorder † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Gastrointestinal disorders                   
Nausea † 1  1/3 (33.33%)  1/11 (9.09%)  1/4 (25.00%)  0/4 (0.00%)  1/19 (5.26%)  3/16 (18.75%)  1/16 (6.25%)  0/16 (0.00%)  2/15 (13.33%) 
Abdominal pain † 1  1/3 (33.33%)  1/11 (9.09%)  1/4 (25.00%)  0/4 (0.00%)  1/19 (5.26%)  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  3/15 (20.00%) 
Small intestinal obstruction † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Ascites † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Diarrhoea † 1  1/3 (33.33%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  2/15 (13.33%) 
Colitis † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  0/15 (0.00%) 
Abdominal distension † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Duodenal stenosis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Enterocolitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Ileus † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Intestinal perforation † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Pancreatitis † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Vomiting † 1  2/3 (66.67%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Constipation † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
General disorders                   
Pyrexia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Pain † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Asthenia † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Multi-organ failure † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Non-cardiac chest pain † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Face oedema † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Fatigue † 1  1/3 (33.33%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Oedema † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Hepatobiliary disorders                   
Hyperbilirubinaemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Infections and infestations                   
Bacteraemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Pneumonia † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Sepsis † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Urinary tract infection † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Lung infection † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Pyelonephritis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Upper respiratory tract infection † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Kidney infection † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Peritonitis † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Vulvitis † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Injury, poisoning and procedural complications                   
Accidental overdose † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Investigations                   
Lipase increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Alanine aminotransferase increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Amylase increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Aspartate aminotransferase increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Blood creatinine increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Platelet count decreased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Liver function test abnormal † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Metabolism and nutrition disorders                   
Decreased appetite † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Dehydration † 1  1/3 (33.33%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Hypercalcaemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Hypokalaemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Hyponatraemia † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders                   
Back pain † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  2/15 (13.33%) 
Arthralgia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Muscular weakness † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Musculoskeletal pain † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                   
Malignant neoplasm progression † 1  1/3 (33.33%)  3/11 (27.27%)  0/4 (0.00%)  0/4 (0.00%)  3/19 (15.79%)  3/16 (18.75%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Brain neoplasm malignant † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Nervous system disorders                   
Cerebral infarction † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Psychiatric disorders                   
Confusional state † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Mental status changes † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Agitation † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Renal and urinary disorders                   
Haematuria † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Hydronephrosis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Renal failure acute † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Urinary tract obstruction † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Reproductive system and breast disorders                   
Vaginal fistula † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Respiratory, thoracic and mediastinal disorders                   
Pleural effusion † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  2/15 (13.33%) 
Hypoxia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Bronchial obstruction † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Pneumonitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Aspiration † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Dyspnoea † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Laryngeal oedema † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Vascular disorders                   
Embolism † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Lymphoedema † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
1
Term from vocabulary, MedDRA (16.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Escalation: 1 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 3 mg/kg Treme Escalation: 3 mg/kg Durva + 1 mg/kg Treme Expansion: Ovarian Cancer Expansion: Colorectal Cancer Expansion: Non-triple Negative Breast Cancer Expansion: Renal Cell Carcinoma Expansion: Cervical Cancer
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   3/3 (100.00%)   11/11 (100.00%)   4/4 (100.00%)   4/4 (100.00%)   19/19 (100.00%)   16/16 (100.00%)   16/16 (100.00%)   16/16 (100.00%)   15/15 (100.00%) 
Blood and lymphatic system disorders                   
Anaemia † 1  2/3 (66.67%)  6/11 (54.55%)  0/4 (0.00%)  1/4 (25.00%)  3/19 (15.79%)  1/16 (6.25%)  3/16 (18.75%)  1/16 (6.25%)  2/15 (13.33%) 
Lymph node pain † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Thrombocytopenia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Lymphadenopathy † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Cardiac disorders                   
Tachycardia † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  2/15 (13.33%) 
Pericardial effusion † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Sinus tachycardia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Palpitations † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Angina pectoris † 1  0/3 (0.00%)  1/11 (9.09%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Ear and labyrinth disorders                   
Ear discomfort † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Tinnitus † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Vertigo † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Endocrine disorders                   
Hypothyroidism † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  3/16 (18.75%)  1/16 (6.25%)  2/16 (12.50%)  2/15 (13.33%) 
Hyperthyroidism † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Adrenal insufficiency † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Hypophysitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Eye disorders                   
Vitreous floaters † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Dry eye † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Lacrimation increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Ocular hyperaemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Vision blurred † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Visual impairment † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Cataract † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Eye irritation † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Gastrointestinal disorders                   
Nausea † 1  0/3 (0.00%)  3/11 (27.27%)  1/4 (25.00%)  1/4 (25.00%)  3/19 (15.79%)  3/16 (18.75%)  6/16 (37.50%)  5/16 (31.25%)  3/15 (20.00%) 
Diarrhoea † 1  1/3 (33.33%)  8/11 (72.73%)  0/4 (0.00%)  2/4 (50.00%)  8/19 (42.11%)  4/16 (25.00%)  7/16 (43.75%)  1/16 (6.25%)  3/15 (20.00%) 
Vomiting † 1  0/3 (0.00%)  5/11 (45.45%)  2/4 (50.00%)  0/4 (0.00%)  7/19 (36.84%)  6/16 (37.50%)  4/16 (25.00%)  2/16 (12.50%)  4/15 (26.67%) 
Constipation † 1  1/3 (33.33%)  5/11 (45.45%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  5/16 (31.25%)  4/16 (25.00%)  3/16 (18.75%)  5/15 (33.33%) 
Abdominal pain † 1  0/3 (0.00%)  1/11 (9.09%)  1/4 (25.00%)  2/4 (50.00%)  3/19 (15.79%)  5/16 (31.25%)  3/16 (18.75%)  0/16 (0.00%)  0/15 (0.00%) 
Dry mouth † 1  0/3 (0.00%)  3/11 (27.27%)  1/4 (25.00%)  0/4 (0.00%)  1/19 (5.26%)  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%)  3/15 (20.00%) 
Ascites † 1  1/3 (33.33%)  1/11 (9.09%)  1/4 (25.00%)  1/4 (25.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Small intestinal obstruction † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Abdominal distension † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  3/16 (18.75%)  0/16 (0.00%)  0/15 (0.00%) 
Gastrooesophageal reflux disease † 1  1/3 (33.33%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  1/15 (6.67%) 
Colitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Abdominal pain upper † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Dysphagia † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Flatulence † 1  1/3 (33.33%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  2/15 (13.33%) 
Abdominal pain lower † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Dyspepsia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  2/4 (50.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Gastrointestinal haemorrhage † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Haematochezia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Haemorrhoids † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Rectal tenesmus † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Retching † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Salivary gland calculus † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Abdominal discomfort † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Toothache † 1  0/3 (0.00%)  1/11 (9.09%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Gastric ulcer † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Mouth ulceration † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Oral pain † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
General disorders                   
Fatigue † 1  1/3 (33.33%)  5/11 (45.45%)  2/4 (50.00%)  3/4 (75.00%)  11/19 (57.89%)  8/16 (50.00%)  7/16 (43.75%)  8/16 (50.00%)  7/15 (46.67%) 
Pyrexia † 1  0/3 (0.00%)  1/11 (9.09%)  1/4 (25.00%)  0/4 (0.00%)  2/19 (10.53%)  2/16 (12.50%)  1/16 (6.25%)  2/16 (12.50%)  5/15 (33.33%) 
Oedema peripheral † 1  2/3 (66.67%)  3/11 (27.27%)  1/4 (25.00%)  0/4 (0.00%)  2/19 (10.53%)  3/16 (18.75%)  3/16 (18.75%)  3/16 (18.75%)  3/15 (20.00%) 
Asthenia † 1  0/3 (0.00%)  4/11 (36.36%)  1/4 (25.00%)  0/4 (0.00%)  2/19 (10.53%)  1/16 (6.25%)  2/16 (12.50%)  0/16 (0.00%)  1/15 (6.67%) 
Chills † 1  1/3 (33.33%)  2/11 (18.18%)  1/4 (25.00%)  1/4 (25.00%)  1/19 (5.26%)  1/16 (6.25%)  1/16 (6.25%)  2/16 (12.50%)  2/15 (13.33%) 
Influenza like illness † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  4/15 (26.67%) 
Malaise † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%)  1/15 (6.67%) 
Device occlusion † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Early satiety † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Infusion site reaction † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Non-cardiac chest pain † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Pain † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Mucosal inflammation † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Swelling † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Irritability † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Localised oedema † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Oedema † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Thirst † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Face oedema † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Tenderness † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Facial pain † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Hepatobiliary disorders                   
Hyperbilirubinaemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Hepatic failure † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Hepatitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Immune system disorders                   
Contrast media allergy † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Drug hypersensitivity † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Seasonal allergy † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Infections and infestations                   
Urinary tract infection † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  2/16 (12.50%)  0/16 (0.00%)  0/16 (0.00%)  5/15 (33.33%) 
Upper respiratory tract infection † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  1/16 (6.25%)  1/16 (6.25%)  1/16 (6.25%)  1/15 (6.67%) 
Pneumonia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Candidiasis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Cystitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  2/15 (13.33%) 
Lung infection † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Oral candidiasis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Abscess oral † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Bacteriuria † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Bronchitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Cellulitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Fungal infection † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Lyme disease † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Onychomycosis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Sinusitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Tinea pedis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Genital herpes † 1  1/3 (33.33%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Herpes zoster † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Mucosal infection † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Pneumonia staphylococcal † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Injury, poisoning and procedural complications                   
Fall † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Contusion † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Fracture † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Procedural pain † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Radius fracture † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Wound † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Acetabulum fracture † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Investigations                   
Aspartate aminotransferase increased † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  1/4 (25.00%)  2/19 (10.53%)  1/16 (6.25%)  4/16 (25.00%)  3/16 (18.75%)  2/15 (13.33%) 
Weight decreased † 1  0/3 (0.00%)  3/11 (27.27%)  0/4 (0.00%)  0/4 (0.00%)  4/19 (21.05%)  3/16 (18.75%)  1/16 (6.25%)  1/16 (6.25%)  2/15 (13.33%) 
Blood alkaline phosphatase increased † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  3/19 (15.79%)  2/16 (12.50%)  2/16 (12.50%)  0/16 (0.00%)  2/15 (13.33%) 
Alanine aminotransferase increased † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  1/4 (25.00%)  1/19 (5.26%)  0/16 (0.00%)  2/16 (12.50%)  2/16 (12.50%)  2/15 (13.33%) 
Blood creatinine increased † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  1/4 (25.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/15 (6.67%) 
Lipase increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Amylase increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Blood bilirubin increased † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
International normalised ratio increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
White blood cell count decreased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  0/15 (0.00%) 
Bilirubin conjugated increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Blood lactate dehydrogenase increased † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Blood potassium decreased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Blood sodium decreased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Blood thyroid stimulating hormone increased † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Neutrophil count increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
White blood cell count increased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Lymphocyte count decreased † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Urine output decreased † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Metabolism and nutrition disorders                   
Decreased appetite † 1  1/3 (33.33%)  5/11 (45.45%)  1/4 (25.00%)  0/4 (0.00%)  4/19 (21.05%)  5/16 (31.25%)  4/16 (25.00%)  5/16 (31.25%)  5/15 (33.33%) 
Dehydration † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  3/16 (18.75%)  3/16 (18.75%)  0/16 (0.00%)  0/15 (0.00%) 
Hypoalbuminaemia † 1  1/3 (33.33%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  2/16 (12.50%)  2/16 (12.50%)  0/16 (0.00%)  1/15 (6.67%) 
Hyponatraemia † 1  1/3 (33.33%)  3/11 (27.27%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  1/16 (6.25%)  2/16 (12.50%)  0/16 (0.00%)  1/15 (6.67%) 
Hypokalaemia † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  3/19 (15.79%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Hypercalcaemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Hyperglycaemia † 1  0/3 (0.00%)  3/11 (27.27%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  1/15 (6.67%) 
Hypocalcaemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  0/15 (0.00%) 
Hyperkalaemia † 1  1/3 (33.33%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Hypernatraemia † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Hypophosphataemia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Polydipsia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Hypomagnesaemia † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders                   
Arthralgia † 1  0/3 (0.00%)  3/11 (27.27%)  0/4 (0.00%)  0/4 (0.00%)  3/19 (15.79%)  2/16 (12.50%)  3/16 (18.75%)  2/16 (12.50%)  1/15 (6.67%) 
Back pain † 1  2/3 (66.67%)  5/11 (45.45%)  1/4 (25.00%)  1/4 (25.00%)  2/19 (10.53%)  2/16 (12.50%)  1/16 (6.25%)  1/16 (6.25%)  1/15 (6.67%) 
Myalgia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  1/16 (6.25%)  0/16 (0.00%)  2/16 (12.50%)  2/15 (13.33%) 
Muscular weakness † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  1/15 (6.67%) 
Muscle spasms † 1  0/3 (0.00%)  1/11 (9.09%)  1/4 (25.00%)  0/4 (0.00%)  3/19 (15.79%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Pain in extremity † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  2/16 (12.50%)  0/15 (0.00%) 
Musculoskeletal chest pain † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Musculoskeletal pain † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Neck pain † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Arthritis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Flank pain † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Joint effusion † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Muscle tightness † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Groin pain † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Joint swelling † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Pathological fracture † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Nervous system disorders                   
Dizziness † 1  1/3 (33.33%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  3/19 (15.79%)  3/16 (18.75%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Dysgeusia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  0/16 (0.00%)  2/15 (13.33%) 
Headache † 1  1/3 (33.33%)  1/11 (9.09%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  2/16 (12.50%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Paraesthesia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Akathisia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Cognitive disorder † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Disturbance in attention † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Dizziness postural † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Hypoaesthesia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Memory impairment † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Monoplegia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Neuralgia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Neuropathy peripheral † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Presyncope † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Sciatica † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Sensory disturbance † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Speech disorder † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Tremor † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Paralysis † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Amnesia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Peripheral sensory neuropathy † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Psychiatric disorders                   
Anxiety † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  3/19 (15.79%)  3/16 (18.75%)  2/16 (12.50%)  0/16 (0.00%)  2/15 (13.33%) 
Insomnia † 1  0/3 (0.00%)  1/11 (9.09%)  1/4 (25.00%)  1/4 (25.00%)  4/19 (21.05%)  3/16 (18.75%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Confusional state † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Depression † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  2/16 (12.50%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Mental status changes † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Euphoric mood † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Agitation † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Renal and urinary disorders                   
Haematuria † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  2/15 (13.33%) 
Bladder spasm † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Dysuria † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  2/15 (13.33%) 
Hydronephrosis † 1  1/3 (33.33%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Proteinuria † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Incontinence † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Nocturia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Pollakiuria † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Pyuria † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Urinary retention † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Urinary tract pain † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Urine abnormality † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Nephrolithiasis † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Urinary incontinence † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Reproductive system and breast disorders                   
Vaginal fistula † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Vaginal haemorrhage † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  2/15 (13.33%) 
Menorrhagia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/15 (6.67%) 
Vaginal discharge † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Pelvic discomfort † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Pelvic pain † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Vaginal disorder † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Vulvovaginal pruritus † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Cough † 1  1/3 (33.33%)  3/11 (27.27%)  1/4 (25.00%)  0/4 (0.00%)  4/19 (21.05%)  2/16 (12.50%)  3/16 (18.75%)  3/16 (18.75%)  2/15 (13.33%) 
Dyspnoea † 1  1/3 (33.33%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  4/19 (21.05%)  2/16 (12.50%)  2/16 (12.50%)  2/16 (12.50%)  2/15 (13.33%) 
Nasal congestion † 1  1/3 (33.33%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  2/16 (12.50%)  1/16 (6.25%)  1/16 (6.25%)  1/15 (6.67%) 
Pleural effusion † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  2/19 (10.53%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Productive cough † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  3/16 (18.75%)  0/15 (0.00%) 
Oropharyngeal pain † 1  0/3 (0.00%)  2/11 (18.18%)  1/4 (25.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  2/15 (13.33%) 
Dysphonia † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Dyspnoea exertional † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Upper-airway cough syndrome † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Emphysema † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Pleuritic pain † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Pulmonary embolism † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Rhinorrhoea † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Epistaxis † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Haemoptysis † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Pneumonitis † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Sinus congestion † 1  1/3 (33.33%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Upper respiratory tract congestion † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Skin and subcutaneous tissue disorders                   
Pruritus † 1  1/3 (33.33%)  2/11 (18.18%)  2/4 (50.00%)  1/4 (25.00%)  4/19 (21.05%)  3/16 (18.75%)  2/16 (12.50%)  3/16 (18.75%)  3/15 (20.00%) 
Rash † 1  2/3 (66.67%)  1/11 (9.09%)  1/4 (25.00%)  0/4 (0.00%)  1/19 (5.26%)  3/16 (18.75%)  0/16 (0.00%)  4/16 (25.00%)  3/15 (20.00%) 
Rash maculo-papular † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  1/4 (25.00%)  4/19 (21.05%)  0/16 (0.00%)  1/16 (6.25%)  5/16 (31.25%)  1/15 (6.67%) 
Dry skin † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  1/16 (6.25%)  2/16 (12.50%)  2/16 (12.50%)  0/15 (0.00%) 
Erythema † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Hyperhidrosis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/15 (6.67%) 
Night sweats † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  2/16 (12.50%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Rash papular † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  1/19 (5.26%)  1/16 (6.25%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Dermatitis acneiform † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/19 (10.53%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Dyshidrotic eczema † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Eczema † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Livedo reticularis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Rash erythematous † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Rash generalised † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Rash pruritic † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Skin exfoliation † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Skin striae † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Swelling face † 1  0/3 (0.00%)  1/11 (9.09%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Vascular disorders                   
Hypotension † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%)  2/15 (13.33%) 
Hot flush † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  1/16 (6.25%)  1/16 (6.25%)  0/15 (0.00%) 
Hypertension † 1  0/3 (0.00%)  2/11 (18.18%)  0/4 (0.00%)  0/4 (0.00%)  1/19 (5.26%)  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Embolism † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
Lymphoedema † 1  0/3 (0.00%)  0/11 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  1/15 (6.67%) 
Thrombophlebitis † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%)  0/15 (0.00%) 
Orthostatic hypotension † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/19 (0.00%)  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%)  0/15 (0.00%) 
Haematoma † 1  0/3 (0.00%)  0/11 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/19 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/16 (0.00%)  0/15 (0.00%) 
1
Term from vocabulary, MedDRA (16.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mary Macri, Director, Clinical Trials Management
Organization: Ludwig Institute for Cancer Research
Phone: (212) 450-1546
EMail: mmacri@lcr.org
Publications:
Layout table for additonal information
Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT01975831    
Other Study ID Numbers: LUD2013-003
First Submitted: October 29, 2013
First Posted: November 5, 2013
Results First Submitted: April 22, 2020
Results First Posted: June 22, 2020
Last Update Posted: July 15, 2021