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An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026)

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ClinicalTrials.gov Identifier: NCT02041533
Recruitment Status : Active, not recruiting
First Posted : January 22, 2014
Results First Posted : July 26, 2017
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Stage IV or Recurrent Non-Small Cell Lung Cancer
Interventions Biological: Nivolumab
Drug: Gemcitabine
Drug: Cisplatin
Drug: Carboplatin
Drug: Paclitaxel
Drug: Pemetrexed
Enrollment 1325

Recruitment Details  
Pre-assignment Details 1325 participants were enrolled; 541 were randomized to a treatment group; 530 were treated. Participants were randomized but not treated due to disease progression (n=2), withdrawal of consent (n=5), or they no longer met study criteria (n=4)
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Period Title: Overall Study
Started 271 270
Began Treatment 267 263
Completed 43 [1] 12 [1]
Not Completed 228 258
Reason Not Completed
Disease Progression             168             142
Study drug toxicity             27             30
Death             1             0
Adverse Event unrelated to study drug             20             21
Subject request to discontinue treatment             5             9
Withdrawal by Subject             2             1
Maximum clinical benefit             0             18
Poor/non-compliance             1             0
Other reasons             0             1
Completed max number of chemo cycles             0             29
Randomized, not treated             4             7
[1]
Completed = Participants continuing in the treatment period
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy Total
Hide Arm/Group Description Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Total of all reporting groups
Overall Number of Baseline Participants 271 270 541
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 271 participants 270 participants 541 participants
62.8  (10.25) 63.4  (9.63) 63.1  (9.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 271 participants 270 participants 541 participants
Female
87
  32.1%
122
  45.2%
209
  38.6%
Male
184
  67.9%
148
  54.8%
332
  61.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 271 participants 270 participants 541 participants
Hispanic or Latino
4
   1.5%
3
   1.1%
7
   1.3%
Not Hispanic or Latino
141
  52.0%
139
  51.5%
280
  51.8%
Unknown or Not Reported
126
  46.5%
128
  47.4%
254
  47.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 271 participants 270 participants 541 participants
American Indian or Alaska Native
1
   0.4%
0
   0.0%
1
   0.2%
Asian
30
  11.1%
17
   6.3%
47
   8.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   2.2%
10
   3.7%
16
   3.0%
White
228
  84.1%
242
  89.6%
470
  86.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
6
   2.2%
1
   0.4%
7
   1.3%
1.Primary Outcome
Title Progression-Free Survival in Participants With PD-L1 Expression >= 5%
Hide Description Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.
Time Frame From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 expression levels >= 5%
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description:
Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Overall Number of Participants Analyzed 211 212
Median (95% Confidence Interval)
Unit of Measure: months
4.21
(2.96 to 5.55)
5.88
(5.42 to 6.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Investigator Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2511
Comments [Not Specified]
Method Log Rank
Comments Log-rank test stratified by histology (squamous vs. non-squamous) as entered into the IVRS.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.91 to 1.45
Estimation Comments Stratified Cox proportional hazard model. Hazard ratio of nivolumab to investigator's choice chemotherapy.
2.Secondary Outcome
Title Progression-Free Survival in All Randomized Participants
Hide Description Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.
Time Frame From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description:
Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Overall Number of Participants Analyzed 271 270
Median (95% Confidence Interval)
Unit of Measure: months
4.21
(3.06 to 5.52)
5.82
(5.42 to 6.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Investigator Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.95 to 1.43
Estimation Comments Stratified Cox proportional hazard model. Hazard ratio of nivolumab to investigator's choice chemotherapy.
3.Secondary Outcome
Title Overall Survival in Participants With PD-L1 Expression >= 5%
Hide Description Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.
Time Frame From date of randomization to date of death (assessed up to August 2016, approximately 28 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 expression >= 5%
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description:
Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Overall Number of Participants Analyzed 211 212
Median (95% Confidence Interval)
Unit of Measure: months
14.36
(11.66 to 17.45)
13.21
(10.68 to 17.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Investigator Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.80 to 1.30
Estimation Comments Stratified Cox proportional hazard model. Hazard ratio of nivolumab to investigator's choice chemotherapy.
4.Secondary Outcome
Title Overall Survival in All Randomized Participants
Hide Description Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.
Time Frame From date of randomization to date of death (assessed up to August 2016, approximately 28 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description:
Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Overall Number of Participants Analyzed 271 270
Median (95% Confidence Interval)
Unit of Measure: months
13.73
(11.76 to 15.41)
13.80
(11.01 to 16.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Investigator Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.86 to 1.33
Estimation Comments Stratified Cox proportional hazard model. Hazard ratio of nivolumab to investigator's choice chemotherapy.
5.Secondary Outcome
Title Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5%
Hide Description ORR was defined as the proportion of randomized participants who achieved a Best Overall Response (BOR) of CR or PR using the RECIST v1.1 criteria per Independent Radiology Review Committee (IRRC) assessment. BOR was defined as the best response designation recorded between the date of randomization and the date of objectively documented progression or start of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. For participants who continued treatment beyond progression, BOR was determined from response designations recorded up to the time of initial progression. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir.
Time Frame From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to August 2016, approximately 28 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 expression >= 5%
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description:
Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Overall Number of Participants Analyzed 211 212
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
26.1
(20.3 to 32.5)
33.5
(27.2 to 40.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Investigator Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.46 to 1.06
Estimation Comments Stratified by histology (squamous vs.non-squamous) at randomization. Strata adjusted odds ratio (Nivolumab over investigator choice of chemotherapy) using Mantel-Haenszel method.
6.Secondary Outcome
Title Duration of Response in Participants With PD-L1 Expression>= 5%
Hide Description Duration of Response (DOR) was summarized for participants with objective response and was defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression as determined by IRRC assessment (per RECIST v1.1) or death due to any cause, whichever occurs first. DOR censoring rules were the same as the PFS primary definition. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir
Time Frame From date of first confirmed response to date of tumor progression (Assessed up to August 2016, approximately 28 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with a confirmed response and PD-L1 expression >= 5%
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description:
Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Overall Number of Participants Analyzed 55 71
Median (Full Range)
Unit of Measure: months
12.12 [1] 
(8.84 to NA)
5.65
(4.21 to 8.51)
[1]
Upper 95% CI was not reached based on Kaplan Meier estimates.
7.Secondary Outcome
Title Time to Response in Participants With PD-L1 Expression >= 5%
Hide Description Time to Response (TTR) was defined as the time from randomization to the date of the first response (CR or PR), as assessed by IRRC assessment. TTR was evaluated for responders only. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir.
Time Frame From date of randomization to date of first confirmed response (assessed up to August 2016, approximately 18 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with a confirmed response and PD-L1 expression >= 5%
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description:
Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Overall Number of Participants Analyzed 55 71
Median (Full Range)
Unit of Measure: months
2.76
(1.2 to 13.2)
2.56
(1.2 to 9.8)
8.Secondary Outcome
Title Disease-related Symptom Improvement Rate by Week 12
Hide Description The Lung Cancer Symptom Score (LCSS) is a validated instrument designed to assess the impact of treatment on disease-related symptoms. It consists of 6 symptom-specific questions related to dyspnea, cough, fatigue, pain, hemoptysis and anorexia plus 3 summary items: symptom distress, interference with activity, and global HRQoL. The degree of impairment was recorded on a 100 mm visual analogue scale with scores from 0 to 100 with zero representing the best score. Disease-related symptom improvement rate by Week 12 is defined as the proportion of all randomized (all PD-L1+) participants who had 10 points or more decrease from baseline in average symptom burden index score at any time between randomization and Week 12.
Time Frame From date of randomization to week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Investigator Choice of Chemotherapy
Hide Arm/Group Description:
Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Investigators' choice of chemotherapy was administered in 3-week cycles for up to 6 cycles:

Squamous:

  • gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
  • gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
  • paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

  • pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
  • pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total).
Overall Number of Participants Analyzed 271 270
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
35.4
(29.7 to 41.4)
33.7
(28.1 to 39.7)
Time Frame From first dose to date of last dose plus 30 days (assessed up to August 2016, approximately 18 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title NIVOLUMAB 3 mg/kg INVESTIGATOR CHOICE
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
NIVOLUMAB 3 mg/kg INVESTIGATOR CHOICE
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
NIVOLUMAB 3 mg/kg INVESTIGATOR CHOICE
Affected / at Risk (%) Affected / at Risk (%)
Total   155/267 (58.05%)   115/263 (43.73%) 
Blood and lymphatic system disorders     
Anaemia  1  0/267 (0.00%)  15/263 (5.70%) 
Febrile neutropenia  1  1/267 (0.37%)  6/263 (2.28%) 
Leukopenia  1  0/267 (0.00%)  1/263 (0.38%) 
Neutropenia  1  0/267 (0.00%)  3/263 (1.14%) 
Pancytopenia  1  1/267 (0.37%)  3/263 (1.14%) 
Thrombocytopenia  1  0/267 (0.00%)  6/263 (2.28%) 
Cardiac disorders     
Acute coronary syndrome  1  2/267 (0.75%)  1/263 (0.38%) 
Acute left ventricular failure  1  1/267 (0.37%)  0/263 (0.00%) 
Atrial fibrillation  1  0/267 (0.00%)  3/263 (1.14%) 
Atrial flutter  1  0/267 (0.00%)  1/263 (0.38%) 
Cardiac arrest  1  1/267 (0.37%)  0/263 (0.00%) 
Cardiac failure  1  0/267 (0.00%)  1/263 (0.38%) 
Cardiac failure acute  1  1/267 (0.37%)  0/263 (0.00%) 
Cardiac failure congestive  1  1/267 (0.37%)  1/263 (0.38%) 
Cardiac tamponade  1  1/267 (0.37%)  0/263 (0.00%) 
Myocardial infarction  1  0/267 (0.00%)  2/263 (0.76%) 
Myocardial ischaemia  1  1/267 (0.37%)  1/263 (0.38%) 
Pericardial effusion  1  0/267 (0.00%)  1/263 (0.38%) 
Sinus bradycardia  1  1/267 (0.37%)  0/263 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  4/267 (1.50%)  2/263 (0.76%) 
Eye disorders     
Cataract  1  1/267 (0.37%)  0/263 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  0/267 (0.00%)  2/263 (0.76%) 
Colitis  1  3/267 (1.12%)  0/263 (0.00%) 
Constipation  1  2/267 (0.75%)  0/263 (0.00%) 
Diarrhoea  1  7/267 (2.62%)  2/263 (0.76%) 
Dysphagia  1  1/267 (0.37%)  0/263 (0.00%) 
Gastrointestinal haemorrhage  1  0/267 (0.00%)  1/263 (0.38%) 
Ileus  1  0/267 (0.00%)  1/263 (0.38%) 
Large intestinal obstruction  1  0/267 (0.00%)  1/263 (0.38%) 
Nausea  1  2/267 (0.75%)  3/263 (1.14%) 
Oesophagitis  1  1/267 (0.37%)  0/263 (0.00%) 
Small intestinal obstruction  1  0/267 (0.00%)  1/263 (0.38%) 
Upper gastrointestinal haemorrhage  1  1/267 (0.37%)  0/263 (0.00%) 
Vomiting  1  2/267 (0.75%)  4/263 (1.52%) 
General disorders     
Asthenia  1  2/267 (0.75%)  0/263 (0.00%) 
Catheter site pain  1  0/267 (0.00%)  1/263 (0.38%) 
Chest pain  1  2/267 (0.75%)  2/263 (0.76%) 
Death  1  1/267 (0.37%)  0/263 (0.00%) 
Fatigue  1  2/267 (0.75%)  5/263 (1.90%) 
General physical health deterioration  1  3/267 (1.12%)  3/263 (1.14%) 
Multiple organ dysfunction syndrome  1  1/267 (0.37%)  0/263 (0.00%) 
Pain  1  1/267 (0.37%)  1/263 (0.38%) 
Performance status decreased  1  0/267 (0.00%)  1/263 (0.38%) 
Pyrexia  1  4/267 (1.50%)  3/263 (1.14%) 
Hepatobiliary disorders     
Cholecystitis acute  1  2/267 (0.75%)  0/263 (0.00%) 
Cholestasis  1  1/267 (0.37%)  1/263 (0.38%) 
Hepatic failure  1  1/267 (0.37%)  0/263 (0.00%) 
Hepatitis  1  1/267 (0.37%)  0/263 (0.00%) 
Immune system disorders     
Hypersensitivity  1  3/267 (1.12%)  0/263 (0.00%) 
Infections and infestations     
Appendicitis  1  0/267 (0.00%)  1/263 (0.38%) 
Appendicitis perforated  1  0/267 (0.00%)  1/263 (0.38%) 
Bronchitis  1  1/267 (0.37%)  2/263 (0.76%) 
Cellulitis  1  0/267 (0.00%)  1/263 (0.38%) 
Diverticulitis  1  1/267 (0.37%)  0/263 (0.00%) 
Erysipelas  1  0/267 (0.00%)  1/263 (0.38%) 
Influenza  1  0/267 (0.00%)  1/263 (0.38%) 
Localised infection  1  0/267 (0.00%)  1/263 (0.38%) 
Lower respiratory tract infection  1  2/267 (0.75%)  0/263 (0.00%) 
Lung infection  1  6/267 (2.25%)  0/263 (0.00%) 
Peritonitis  1  0/267 (0.00%)  1/263 (0.38%) 
Pneumonia  1  10/267 (3.75%)  17/263 (6.46%) 
Pneumonia bacterial  1  0/267 (0.00%)  1/263 (0.38%) 
Respiratory tract infection  1  1/267 (0.37%)  1/263 (0.38%) 
Sepsis  1  4/267 (1.50%)  1/263 (0.38%) 
Septic shock  1  1/267 (0.37%)  1/263 (0.38%) 
Skin infection  1  0/267 (0.00%)  1/263 (0.38%) 
Subcutaneous abscess  1  1/267 (0.37%)  0/263 (0.00%) 
Upper respiratory tract infection  1  1/267 (0.37%)  0/263 (0.00%) 
Urinary tract infection  1  3/267 (1.12%)  0/263 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  1/267 (0.37%)  1/263 (0.38%) 
Femur fracture  1  0/267 (0.00%)  2/263 (0.76%) 
Hip fracture  1  2/267 (0.75%)  0/263 (0.00%) 
Infusion related reaction  1  2/267 (0.75%)  0/263 (0.00%) 
Kyphosis postoperative  1  0/267 (0.00%)  1/263 (0.38%) 
Lumbar vertebral fracture  1  0/267 (0.00%)  1/263 (0.38%) 
Procedural complication  1  0/267 (0.00%)  1/263 (0.38%) 
Radiation necrosis  1  1/267 (0.37%)  0/263 (0.00%) 
Radiation pneumonitis  1  1/267 (0.37%)  0/263 (0.00%) 
Upper limb fracture  1  0/267 (0.00%)  1/263 (0.38%) 
Investigations     
Alanine aminotransferase increased  1  5/267 (1.87%)  0/263 (0.00%) 
Aspartate aminotransferase increased  1  6/267 (2.25%)  0/263 (0.00%) 
Blood alkaline phosphatase increased  1  1/267 (0.37%)  0/263 (0.00%) 
Blood bilirubin increased  1  1/267 (0.37%)  0/263 (0.00%) 
Blood creatinine increased  1  1/267 (0.37%)  1/263 (0.38%) 
C-reactive protein increased  1  0/267 (0.00%)  1/263 (0.38%) 
Gamma-glutamyltransferase increased  1  2/267 (0.75%)  0/263 (0.00%) 
Haemoglobin decreased  1  0/267 (0.00%)  1/263 (0.38%) 
Transaminases increased  1  1/267 (0.37%)  1/263 (0.38%) 
Metabolism and nutrition disorders     
Dehydration  1  4/267 (1.50%)  2/263 (0.76%) 
Hypercalcaemia  1  3/267 (1.12%)  0/263 (0.00%) 
Hyperglycaemia  1  2/267 (0.75%)  0/263 (0.00%) 
Hypoglycaemia  1  1/267 (0.37%)  0/263 (0.00%) 
Hypokalaemia  1  1/267 (0.37%)  0/263 (0.00%) 
Hyponatraemia  1  4/267 (1.50%)  1/263 (0.38%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  2/267 (0.75%)  0/263 (0.00%) 
Bone pain  1  1/267 (0.37%)  2/263 (0.76%) 
Osteolysis  1  0/267 (0.00%)  1/263 (0.38%) 
Pathological fracture  1  2/267 (0.75%)  0/263 (0.00%) 
Polyarthritis  1  1/267 (0.37%)  0/263 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  4/267 (1.50%)  1/263 (0.38%) 
Haemangioblastoma  1  1/267 (0.37%)  0/263 (0.00%) 
Lung neoplasm malignant  1  2/267 (0.75%)  0/263 (0.00%) 
Malignant melanoma  1  0/267 (0.00%)  1/263 (0.38%) 
Malignant neoplasm of spinal cord  1  1/267 (0.37%)  0/263 (0.00%) 
Malignant neoplasm progression  1  35/267 (13.11%)  12/263 (4.56%) 
Malignant pleural effusion  1  4/267 (1.50%)  2/263 (0.76%) 
Metastases to central nervous system  1  2/267 (0.75%)  2/263 (0.76%) 
Metastases to meninges  1  1/267 (0.37%)  0/263 (0.00%) 
Metastases to spine  1  3/267 (1.12%)  0/263 (0.00%) 
Non-small cell lung cancer  1  1/267 (0.37%)  0/263 (0.00%) 
Pericardial effusion malignant  1  5/267 (1.87%)  1/263 (0.38%) 
Tumour pain  1  4/267 (1.50%)  0/263 (0.00%) 
Nervous system disorders     
Aphasia  1  1/267 (0.37%)  0/263 (0.00%) 
Ataxia  1  0/267 (0.00%)  1/263 (0.38%) 
Cerebrovascular accident  1  2/267 (0.75%)  1/263 (0.38%) 
Depressed level of consciousness  1  1/267 (0.37%)  0/263 (0.00%) 
Epilepsy  1  1/267 (0.37%)  0/263 (0.00%) 
Headache  1  1/267 (0.37%)  0/263 (0.00%) 
Loss of consciousness  1  0/267 (0.00%)  1/263 (0.38%) 
Muscle spasticity  1  1/267 (0.37%)  0/263 (0.00%) 
Presyncope  1  0/267 (0.00%)  1/263 (0.38%) 
Seizure  1  2/267 (0.75%)  1/263 (0.38%) 
Spinal cord compression  1  0/267 (0.00%)  1/263 (0.38%) 
Syncope  1  2/267 (0.75%)  3/263 (1.14%) 
Vocal cord paralysis  1  0/267 (0.00%)  1/263 (0.38%) 
Psychiatric disorders     
Confusional state  1  2/267 (0.75%)  1/263 (0.38%) 
Mental status changes  1  1/267 (0.37%)  0/263 (0.00%) 
Psychotic disorder  1  1/267 (0.37%)  0/263 (0.00%) 
Suicide attempt  1  1/267 (0.37%)  0/263 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/267 (0.37%)  0/263 (0.00%) 
Haematuria  1  1/267 (0.37%)  0/263 (0.00%) 
Renal failure  1  2/267 (0.75%)  0/263 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/267 (0.00%)  1/263 (0.38%) 
Atelectasis  1  1/267 (0.37%)  0/263 (0.00%) 
Bronchial obstruction  1  0/267 (0.00%)  1/263 (0.38%) 
Chronic obstructive pulmonary disease  1  3/267 (1.12%)  6/263 (2.28%) 
Dyspnoea  1  3/267 (1.12%)  3/263 (1.14%) 
Eosinophilic pneumonia  1  1/267 (0.37%)  0/263 (0.00%) 
Haemoptysis  1  0/267 (0.00%)  1/263 (0.38%) 
Haemothorax  1  0/267 (0.00%)  1/263 (0.38%) 
Interstitial lung disease  1  1/267 (0.37%)  0/263 (0.00%) 
Mediastinal disorder  1  1/267 (0.37%)  0/263 (0.00%) 
Pleural effusion  1  6/267 (2.25%)  2/263 (0.76%) 
Pleuritic pain  1  0/267 (0.00%)  1/263 (0.38%) 
Pneumonia aspiration  1  1/267 (0.37%)  0/263 (0.00%) 
Pneumonitis  1  7/267 (2.62%)  0/263 (0.00%) 
Pneumothorax  1  3/267 (1.12%)  0/263 (0.00%) 
Pulmonary embolism  1  5/267 (1.87%)  5/263 (1.90%) 
Pulmonary haemorrhage  1  2/267 (0.75%)  1/263 (0.38%) 
Pulmonary microemboli  1  1/267 (0.37%)  0/263 (0.00%) 
Pulmonary oedema  1  0/267 (0.00%)  1/263 (0.38%) 
Respiratory failure  1  4/267 (1.50%)  0/263 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/267 (0.37%)  0/263 (0.00%) 
Rash maculo-papular  1  1/267 (0.37%)  0/263 (0.00%) 
Rash papular  1  1/267 (0.37%)  0/263 (0.00%) 
Stevens-johnson syndrome  1  1/267 (0.37%)  0/263 (0.00%) 
Vascular disorders     
Air embolism  1  1/267 (0.37%)  0/263 (0.00%) 
Aortic aneurysm rupture  1  1/267 (0.37%)  0/263 (0.00%) 
Circulatory collapse  1  0/267 (0.00%)  2/263 (0.76%) 
Deep vein thrombosis  1  3/267 (1.12%)  0/263 (0.00%) 
Embolism  1  0/267 (0.00%)  3/263 (1.14%) 
Hypotension  1  1/267 (0.37%)  0/263 (0.00%) 
Iliac artery occlusion  1  0/267 (0.00%)  1/263 (0.38%) 
Jugular vein thrombosis  1  1/267 (0.37%)  0/263 (0.00%) 
Peripheral artery thrombosis  1  0/267 (0.00%)  1/263 (0.38%) 
Superior vena cava syndrome  1  0/267 (0.00%)  2/263 (0.76%) 
Vascular occlusion  1  0/267 (0.00%)  1/263 (0.38%) 
Vein disorder  1  1/267 (0.37%)  0/263 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
NIVOLUMAB 3 mg/kg INVESTIGATOR CHOICE
Affected / at Risk (%) Affected / at Risk (%)
Total   238/267 (89.14%)   248/263 (94.30%) 
Blood and lymphatic system disorders     
Anaemia  1  38/267 (14.23%)  127/263 (48.29%) 
Leukopenia  1  1/267 (0.37%)  16/263 (6.08%) 
Neutropenia  1  2/267 (0.75%)  51/263 (19.39%) 
Thrombocytopenia  1  4/267 (1.50%)  38/263 (14.45%) 
Endocrine disorders     
Hypothyroidism  1  20/267 (7.49%)  7/263 (2.66%) 
Eye disorders     
Lacrimation increased  1  3/267 (1.12%)  21/263 (7.98%) 
Gastrointestinal disorders     
Abdominal pain  1  26/267 (9.74%)  21/263 (7.98%) 
Constipation  1  52/267 (19.48%)  68/263 (25.86%) 
Diarrhoea  1  67/267 (25.09%)  60/263 (22.81%) 
Dyspepsia  1  17/267 (6.37%)  11/263 (4.18%) 
Nausea  1  78/267 (29.21%)  134/263 (50.95%) 
Stomatitis  1  8/267 (3.00%)  16/263 (6.08%) 
Vomiting  1  54/267 (20.22%)  65/263 (24.71%) 
General disorders     
Asthenia  1  21/267 (7.87%)  37/263 (14.07%) 
Chest pain  1  9/267 (3.37%)  14/263 (5.32%) 
Chills  1  16/267 (5.99%)  12/263 (4.56%) 
Fatigue  1  102/267 (38.20%)  115/263 (43.73%) 
Mucosal inflammation  1  6/267 (2.25%)  21/263 (7.98%) 
Non-cardiac chest pain  1  24/267 (8.99%)  10/263 (3.80%) 
Oedema peripheral  1  30/267 (11.24%)  44/263 (16.73%) 
Pyrexia  1  33/267 (12.36%)  39/263 (14.83%) 
Infections and infestations     
Nasopharyngitis  1  17/267 (6.37%)  12/263 (4.56%) 
Upper respiratory tract infection  1  18/267 (6.74%)  12/263 (4.56%) 
Investigations     
Alanine aminotransferase increased  1  25/267 (9.36%)  18/263 (6.84%) 
Aspartate aminotransferase increased  1  34/267 (12.73%)  18/263 (6.84%) 
Blood alkaline phosphatase increased  1  17/267 (6.37%)  12/263 (4.56%) 
Blood creatinine increased  1  10/267 (3.75%)  18/263 (6.84%) 
Lymphocyte count decreased  1  17/267 (6.37%)  16/263 (6.08%) 
Neutrophil count decreased  1  2/267 (0.75%)  41/263 (15.59%) 
Platelet count decreased  1  4/267 (1.50%)  36/263 (13.69%) 
Weight decreased  1  37/267 (13.86%)  24/263 (9.13%) 
White blood cell count decreased  1  4/267 (1.50%)  29/263 (11.03%) 
Metabolism and nutrition disorders     
Decreased appetite  1  76/267 (28.46%)  81/263 (30.80%) 
Hyperglycaemia  1  15/267 (5.62%)  13/263 (4.94%) 
Hypoalbuminaemia  1  25/267 (9.36%)  19/263 (7.22%) 
Hypokalaemia  1  18/267 (6.74%)  15/263 (5.70%) 
Hypomagnesaemia  1  13/267 (4.87%)  38/263 (14.45%) 
Hyponatraemia  1  24/267 (8.99%)  25/263 (9.51%) 
Hypophosphataemia  1  7/267 (2.62%)  14/263 (5.32%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  35/267 (13.11%)  17/263 (6.46%) 
Back pain  1  34/267 (12.73%)  33/263 (12.55%) 
Muscular weakness  1  12/267 (4.49%)  19/263 (7.22%) 
Musculoskeletal chest pain  1  16/267 (5.99%)  6/263 (2.28%) 
Musculoskeletal pain  1  19/267 (7.12%)  9/263 (3.42%) 
Myalgia  1  26/267 (9.74%)  15/263 (5.70%) 
Pain in extremity  1  17/267 (6.37%)  17/263 (6.46%) 
Nervous system disorders     
Dizziness  1  26/267 (9.74%)  25/263 (9.51%) 
Dysgeusia  1  14/267 (5.24%)  24/263 (9.13%) 
Headache  1  24/267 (8.99%)  31/263 (11.79%) 
Peripheral sensory neuropathy  1  6/267 (2.25%)  18/263 (6.84%) 
Psychiatric disorders     
Insomnia  1  17/267 (6.37%)  19/263 (7.22%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  67/267 (25.09%)  49/263 (18.63%) 
Dysphonia  1  9/267 (3.37%)  16/263 (6.08%) 
Dyspnoea  1  64/267 (23.97%)  40/263 (15.21%) 
Epistaxis  1  5/267 (1.87%)  17/263 (6.46%) 
Haemoptysis  1  15/267 (5.62%)  12/263 (4.56%) 
Productive cough  1  27/267 (10.11%)  14/263 (5.32%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  5/267 (1.87%)  24/263 (9.13%) 
Dry skin  1  17/267 (6.37%)  11/263 (4.18%) 
Pruritus  1  34/267 (12.73%)  13/263 (4.94%) 
Rash  1  32/267 (11.99%)  20/263 (7.60%) 
Rash maculo-papular  1  14/267 (5.24%)  7/263 (2.66%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02041533     History of Changes
Other Study ID Numbers: CA209-026
2012-004502-93 ( EudraCT Number )
First Submitted: January 19, 2014
First Posted: January 22, 2014
Results First Submitted: June 26, 2017
Results First Posted: July 26, 2017
Last Update Posted: February 14, 2018