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Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC (CheckMate057)

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ClinicalTrials.gov Identifier: NCT01673867
Recruitment Status : Active, not recruiting
First Posted : August 28, 2012
Results First Posted : February 26, 2016
Last Update Posted : April 10, 2018
Sponsor:
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 Non-Squamous Cell Non-small Cell Lung Cancer
Interventions Biological: Nivolumab
Drug: Docetaxel
Enrollment 792

Recruitment Details  
Pre-assignment Details A total of 792 participants enrolled in the study; 582 were randomized. Of the 210 participants not randomized, 4 experienced an adverse event (AE), 24 withdrew consent, 5 died, 1 was lost to follow-up, 163 no longer met study criteria, 1 was removed by sponsor for administrative reasons, and 12 were removed for other reasons. Study is ongoing.
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends. Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Period Title: Randomization
Started 292 290
Completed 287 268
Not Completed 5 22
Reason Not Completed
AE unrelated to study drug             1             0
Requested treatment discontinuation             0             4
Withdrawal by Subject             0             12
Lost to Follow-up             0             1
No longer meets criteria             4             5
Period Title: Treatment
Started 287 268
Completed 43 0
Not Completed 244 268
Reason Not Completed
Disease Progression             194             179
Study Drug Toxicity             17             42
Death             1             1
AE unrelated to study drug             19             11
Requested treatment discontinuation             5             16
Withdrawal by Subject             4             6
Maximum clinical benefit             0             10
No longer meets criteria             2             0
Required steroid therapy             1             0
Health status not improved             1             0
Required prolonged hospitalization             0             1
Symptomatic deterioration             0             1
Physician Decision             0             1
Arm/Group Title Nivolumab Docetaxel Total
Hide Arm/Group Description Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends. Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends. Total of all reporting groups
Overall Number of Baseline Participants 292 290 582
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 292 participants 290 participants 582 participants
60.9  (9.27) 62.3  (9.75) 61.6  (9.53)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 292 participants 290 participants 582 participants
< 65 184 155 339
>= 65 AND < 75 88 112 200
>= 75 AND < 85 20 21 41
>= 85 0 2 2
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 292 participants 290 participants 582 participants
Female
141
  48.3%
122
  42.1%
263
  45.2%
Male
151
  51.7%
168
  57.9%
319
  54.8%
PD-L1 Expression  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 292 participants 290 participants 582 participants
PD-L1 not quantifiable at baseline 61 66 127
PD-L1 expression <1% 108 101 209
PD-L1 expression >=1% 123 123 246
1.Primary Outcome
Title Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint
Hide Description OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
Time Frame Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Median (95% Confidence Interval)
Unit of Measure: months
12.19
(9.66 to 14.98)
9.36
(8.05 to 10.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95.92%
0.59 to 0.89
Estimation Comments HR = Nivolumab over docetaxel
2.Primary Outcome
Title One-year Overall Survival (OS) Rate in All Randomized Participants
Hide Description The one-year overall survival rate is a percentage, representing the fraction of all randomized participants who were alive following one year of treatment. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50.5
(44.6 to 56.1)
39.0
(33.3 to 44.6)
3.Primary Outcome
Title Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint
Hide Description The number of participants who died from any cause was reported for each arm. Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
Time Frame Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Measure Type: Number
Unit of Measure: participants
190 223
4.Secondary Outcome
Title Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint
Hide Description

ORR was defined as the percentage of participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). BOR was defined as the best investigator-assessed response designation, recorded between the date of randomization and the date of objectively documented progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or the date of subsequent anti-cancer therapy (excluding on-treatment palliative radiotherapy of non-target bone lesions or Central Nervous System (CNS) lesions), whichever occurred first.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CIs were computed using the Clopper and Pearson method.

Time Frame Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
19.2
(14.8 to 24.2)
12.4
(8.8 to 16.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0246
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.68
Confidence Interval (2-Sided) 95%
1.07 to 2.64
Estimation Comments Odds Ratio = Nivolumab over docetaxel
5.Secondary Outcome
Title Duration of Objective Response (DOR) in Months for All Confirmed Responders at Primary Endpoint
Hide Description

DOR was defined as the time from the date of first confirmed response to the date of the first documented tumor progression (per RECIST v1.1), as determined by the investigator, or death due to any cause, whichever occurred first. DOR was evaluated only for confirmed responders (i.e. participants with confirmed CR or PR).

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters.

Participants who neither progressed nor died were censored on the date of their last evaluable tumor assessment.

Time Frame Date of confirmed response to date of documented tumor progression or death, up to March 2015 (approximately 29 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who demonstrate partial response (PR) or complete response (CR).
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 56 36
Median (Full Range)
Unit of Measure: months
17.15
(1.8 to 22.6)
5.55
(1.2 to 15.2)
6.Secondary Outcome
Title Time To Response (TTR) in Months for All Confirmed Responders at Primary Endpoint
Hide Description Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters.
Time Frame Randomization until confirmed response, up to March 2015 (approximately 29 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who demonstrate partial response or complete response
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 56 36
Median (Full Range)
Unit of Measure: months
2.10
(1.2 to 8.6)
2.61
(1.4 to 6.3)
7.Secondary Outcome
Title Progression-Free Survival (PFS) Rate at 12 Months
Hide Description PFS rate was defined as the percentage of participants experiencing no disease progression or death from any cause at 12 months after randomization. Progression was assessed by investigators according to RECIST v1.1. 95% CIs were estimated using the Kaplan-Meier method.
Time Frame Randomization to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.5
(14.1 to 23.4)
8.1
(5.1 to 12.0)
8.Secondary Outcome
Title Progression-Free Survival (PFS) Time in Months for All Randomized Participants at Primary Endpoint
Hide Description PFS was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator per RECIST v1.1 criteria, or death due to any cause. Participants underwent radiographic tumor assessments every 6 weeks (+/- 5 days) from week 9 (+/- 5 days) for the first year on treatment, then every 12 weeks after the first year on treatment until documented disease progression. The PFS curves were estimated using KM method. Two-sided 95% CIs for median PFS were computed by Brookmeyer and Crowley method (using log-log transformation). Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
Time Frame Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Median (95% Confidence Interval)
Unit of Measure: months
2.33
(2.17 to 3.32)
4.21
(3.45 to 4.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3932
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.77 to 1.11
Estimation Comments HR = Nivolumab over docetaxel
9.Secondary Outcome
Title Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12
Hide Description Disease-related symptom improvement rate by Week 12 was defined as the percentage of randomized participants who had a 10 point or greater decrease from baseline in average symptom burden index score at any time between randomization and Week 12. The participant portion of the Lung Cancer Symptom Scale (LCSS) consisted of 6 symptom-specific questions that addressed cough, dyspnea, fatigue, pain, hemoptysis, and anorexia, plus 3 summary items on symptom distress, interference with activity level, and global health-related Quality of Life (QoL). The scores range from 0 to 100, with 0 representing the best possible score and 100 being the worst possible score. The average symptom burden index score at each assessment was defined as the mean of the 6 symptom-specific questions of the LCSS. 95% CIs were computed using Clopper-Pearson Method.
Time Frame Randomization to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.8
(13.6 to 22.7)
19.7
(15.2 to 24.7)
10.Secondary Outcome
Title Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint
Hide Description Overall Survival time was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
Time Frame Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Median (95% Confidence Interval)
Unit of Measure: months
PD-L1 >= 1% (n=123,123)
17.15
(12.09 to 20.63)
9.00
(7.10 to 10.55)
PD-L1 <1% (n=108, 101)
10.41
(7.29 to 14.26)
10.09
(7.36 to 11.93)
PD-L1 not quantifiable at baseline (n=61, 66)
9.20
(5.91 to 12.75)
10.48
(7.20 to 13.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression >= 1%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.43 to 0.82
Estimation Comments Hazard Ratio (95% CI) Nivolumab 3mg/kg over Docetaxel : PD-L1 expression >= 1%
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression < 1%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.66 to 1.24
Estimation Comments Hazard Ratio (95% CI) Nivolumab 3mg/kg over Docetaxel: PD-L1 expression < 1%
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression not quantifiable at baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.61 to 1.35
Estimation Comments Hazard Ratio (95% CI) : Nivolumab 3mg/kg over Docetaxel : PD-L1 expression not quantifiable at baseline
11.Secondary Outcome
Title Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint
Hide Description ORR was reported for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CIs were computed using the Clopper and Pearson method.
Time Frame Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 292 290
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
PD-L1 >=1% (n= 123,123)
30.9
(22.9 to 39.9)
12.2
(7.0 to 19.3)
PD-L1 <1% (n= 108,101)
9.3
(4.5 to 16.4)
14.9
(8.6 to 23.3)
PD-L1 not quantifiable at baseline (n= 61,66)
13.1
(5.8 to 24.2)
9.1
(3.4 to 18.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression >= 1%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.22
Confidence Interval (2-Sided) 95%
1.60 to 6.71
Estimation Comments Odds Ratio (95% CI) Nivolumab 3mg/kg over Docetaxel : PD-L1 expression >= 1%
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression < 1%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.22 to 1.48
Estimation Comments Odds Ratio (95% CI) Nivolumab 3mg/kg over Docetaxel : PD-L1 expression < 1%
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression not quantifiable at baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
0.43 to 5.63
Estimation Comments Odds Ratio (95% CI) Nivolumab 3mg/kg over Docetaxel : PD-L1 expression not quantifiable at baseline
Time Frame From first dose to last dose plus 30 days up to Primary Endpoint (February 2015)
Adverse Event Reporting Description Study initiated: October 2012 Primary Endpoint: February 2015
 
Arm/Group Title DOCETAXEL NIVOLUMAB 3 mg/kg
Hide Arm/Group Description Docetaxel 75 mg/m^2 concentrate for solution for intravenous (IV) infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends. Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
All-Cause Mortality
DOCETAXEL NIVOLUMAB 3 mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DOCETAXEL NIVOLUMAB 3 mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   111/268 (41.42%)   134/287 (46.69%) 
Blood and lymphatic system disorders     
Haematotoxicity  1  1/268 (0.37%)  0/287 (0.00%) 
Febrile neutropenia  1  24/268 (8.96%)  0/287 (0.00%) 
Anaemia  1  4/268 (1.49%)  2/287 (0.70%) 
Leukopenia  1  1/268 (0.37%)  0/287 (0.00%) 
Neutropenia  1  8/268 (2.99%)  0/287 (0.00%) 
Cardiac disorders     
Cardiac arrest  1  0/268 (0.00%)  1/287 (0.35%) 
Atrial fibrillation  1  2/268 (0.75%)  2/287 (0.70%) 
Pericardial effusion  1  3/268 (1.12%)  2/287 (0.70%) 
Sick sinus syndrome  1  0/268 (0.00%)  1/287 (0.35%) 
Cardiopulmonary failure  1  0/268 (0.00%)  1/287 (0.35%) 
Pericarditis  1  1/268 (0.37%)  0/287 (0.00%) 
Atrial flutter  1  1/268 (0.37%)  1/287 (0.35%) 
Cardiac tamponade  1  1/268 (0.37%)  1/287 (0.35%) 
Ear and labyrinth disorders     
Vertigo  1  1/268 (0.37%)  0/287 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  0/268 (0.00%)  1/287 (0.35%) 
Eye disorders     
Retinal tear  1  0/268 (0.00%)  1/287 (0.35%) 
Gastrointestinal disorders     
Ascites  1  0/268 (0.00%)  2/287 (0.70%) 
Gastrointestinal haemorrhage  1  1/268 (0.37%)  0/287 (0.00%) 
Intestinal perforation  1  0/268 (0.00%)  1/287 (0.35%) 
Abdominal pain  1  2/268 (0.75%)  1/287 (0.35%) 
Inguinal hernia  1  0/268 (0.00%)  1/287 (0.35%) 
Large intestine perforation  1  1/268 (0.37%)  0/287 (0.00%) 
Nausea  1  2/268 (0.75%)  4/287 (1.39%) 
Dysphagia  1  0/268 (0.00%)  1/287 (0.35%) 
Haematemesis  1  1/268 (0.37%)  1/287 (0.35%) 
Colitis  1  0/268 (0.00%)  2/287 (0.70%) 
Stomatitis  1  0/268 (0.00%)  1/287 (0.35%) 
Diarrhoea  1  1/268 (0.37%)  3/287 (1.05%) 
Vomiting  1  1/268 (0.37%)  0/287 (0.00%) 
Abdominal pain upper  1  0/268 (0.00%)  1/287 (0.35%) 
Small intestinal obstruction  1  1/268 (0.37%)  0/287 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/268 (0.37%)  0/287 (0.00%) 
General disorders     
Sudden death  1  2/268 (0.75%)  1/287 (0.35%) 
Non-cardiac chest pain  1  1/268 (0.37%)  2/287 (0.70%) 
Gait disturbance  1  0/268 (0.00%)  1/287 (0.35%) 
General physical health deterioration  1  3/268 (1.12%)  4/287 (1.39%) 
Inflammation  1  0/268 (0.00%)  1/287 (0.35%) 
Malaise  1  1/268 (0.37%)  0/287 (0.00%) 
Pyrexia  1  4/268 (1.49%)  4/287 (1.39%) 
Disease progression  1  1/268 (0.37%)  0/287 (0.00%) 
Medical device complication  1  0/268 (0.00%)  1/287 (0.35%) 
Multi-organ failure  1  0/268 (0.00%)  1/287 (0.35%) 
Pain  1  3/268 (1.12%)  5/287 (1.74%) 
Asthenia  1  3/268 (1.12%)  3/287 (1.05%) 
Fatigue  1  2/268 (0.75%)  1/287 (0.35%) 
Mucosal inflammation  1  1/268 (0.37%)  0/287 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  0/268 (0.00%)  1/287 (0.35%) 
Hepatotoxicity  1  0/268 (0.00%)  1/287 (0.35%) 
Infections and infestations     
Clostridium difficile colitis  1  1/268 (0.37%)  0/287 (0.00%) 
Device related infection  1  0/268 (0.00%)  2/287 (0.70%) 
Pneumonia  1  13/268 (4.85%)  12/287 (4.18%) 
Pneumonia necrotising  1  1/268 (0.37%)  0/287 (0.00%) 
Sepsis  1  1/268 (0.37%)  0/287 (0.00%) 
Upper respiratory tract infection  1  1/268 (0.37%)  0/287 (0.00%) 
Urinary tract infection  1  1/268 (0.37%)  1/287 (0.35%) 
Bronchopneumonia  1  0/268 (0.00%)  1/287 (0.35%) 
Infected skin ulcer  1  0/268 (0.00%)  1/287 (0.35%) 
Pneumonia mycoplasmal  1  1/268 (0.37%)  0/287 (0.00%) 
Bronchitis  1  3/268 (1.12%)  3/287 (1.05%) 
Cellulitis  1  1/268 (0.37%)  1/287 (0.35%) 
Lung infection  1  1/268 (0.37%)  0/287 (0.00%) 
Infection  1  1/268 (0.37%)  1/287 (0.35%) 
Pneumonia bacterial  1  0/268 (0.00%)  2/287 (0.70%) 
Post procedural pneumonia  1  1/268 (0.37%)  0/287 (0.00%) 
Septic shock  1  1/268 (0.37%)  0/287 (0.00%) 
Lobar pneumonia  1  1/268 (0.37%)  0/287 (0.00%) 
Nail infection  1  1/268 (0.37%)  0/287 (0.00%) 
Peritonitis bacterial  1  0/268 (0.00%)  1/287 (0.35%) 
Encephalitis  1  0/268 (0.00%)  1/287 (0.35%) 
Respiratory tract infection  1  3/268 (1.12%)  1/287 (0.35%) 
Injury, poisoning and procedural complications     
Head injury  1  0/268 (0.00%)  1/287 (0.35%) 
Radius fracture  1  0/268 (0.00%)  1/287 (0.35%) 
Infusion related reaction  1  0/268 (0.00%)  2/287 (0.70%) 
Wrist fracture  1  0/268 (0.00%)  1/287 (0.35%) 
Thoracic vertebral fracture  1  2/268 (0.75%)  0/287 (0.00%) 
Investigations     
Neutrophil count decreased  1  1/268 (0.37%)  0/287 (0.00%) 
Transaminases increased  1  0/268 (0.00%)  1/287 (0.35%) 
Blood creatinine increased  1  0/268 (0.00%)  1/287 (0.35%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  1/268 (0.37%)  0/287 (0.00%) 
Dehydration  1  4/268 (1.49%)  0/287 (0.00%) 
Hyperglycaemia  1  0/268 (0.00%)  1/287 (0.35%) 
Hyponatraemia  1  1/268 (0.37%)  1/287 (0.35%) 
Musculoskeletal and connective tissue disorders     
Osteoporotic fracture  1  0/268 (0.00%)  1/287 (0.35%) 
Polymyalgia rheumatica  1  0/268 (0.00%)  1/287 (0.35%) 
Pathological fracture  1  1/268 (0.37%)  0/287 (0.00%) 
Osteonecrosis  1  0/268 (0.00%)  1/287 (0.35%) 
Pain in extremity  1  1/268 (0.37%)  1/287 (0.35%) 
Arthralgia  1  0/268 (0.00%)  1/287 (0.35%) 
Osteonecrosis of jaw  1  0/268 (0.00%)  1/287 (0.35%) 
Musculoskeletal pain  1  0/268 (0.00%)  1/287 (0.35%) 
Fistula  1  0/268 (0.00%)  1/287 (0.35%) 
Musculoskeletal chest pain  1  0/268 (0.00%)  1/287 (0.35%) 
Osteoporosis  1  0/268 (0.00%)  1/287 (0.35%) 
Back pain  1  3/268 (1.12%)  2/287 (0.70%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant  1  0/268 (0.00%)  1/287 (0.35%) 
Metastases to central nervous system  1  1/268 (0.37%)  3/287 (1.05%) 
Neoplasm progression  1  0/268 (0.00%)  1/287 (0.35%) 
Metastases to bone  1  1/268 (0.37%)  1/287 (0.35%) 
Ovarian neoplasm  1  0/268 (0.00%)  1/287 (0.35%) 
Breast cancer  1  0/268 (0.00%)  2/287 (0.70%) 
Cancer pain  1  0/268 (0.00%)  1/287 (0.35%) 
Lymphangiosis carcinomatosa  1  0/268 (0.00%)  1/287 (0.35%) 
Metastases to spine  1  0/268 (0.00%)  1/287 (0.35%) 
Non-small cell lung cancer  1  1/268 (0.37%)  2/287 (0.70%) 
Pancreatic carcinoma  1  0/268 (0.00%)  1/287 (0.35%) 
Metastases to meninges  1  0/268 (0.00%)  1/287 (0.35%) 
Bladder transitional cell carcinoma  1  0/268 (0.00%)  1/287 (0.35%) 
Non-small cell lung cancer metastatic  1  1/268 (0.37%)  0/287 (0.00%) 
Malignant neoplasm progression  1  7/268 (2.61%)  23/287 (8.01%) 
Malignant pleural effusion  1  0/268 (0.00%)  1/287 (0.35%) 
Pericardial effusion malignant  1  0/268 (0.00%)  1/287 (0.35%) 
Nervous system disorders     
Syncope  1  0/268 (0.00%)  1/287 (0.35%) 
Neuralgia  1  0/268 (0.00%)  1/287 (0.35%) 
Hemiplegia  1  0/268 (0.00%)  1/287 (0.35%) 
Hydrocephalus  1  0/268 (0.00%)  1/287 (0.35%) 
Carotid artery stenosis  1  0/268 (0.00%)  1/287 (0.35%) 
Cerebrovascular accident  1  0/268 (0.00%)  1/287 (0.35%) 
Headache  1  0/268 (0.00%)  4/287 (1.39%) 
Somnolence  1  1/268 (0.37%)  1/287 (0.35%) 
Spinal cord compression  1  1/268 (0.37%)  0/287 (0.00%) 
Psychiatric disorders     
Depression  1  0/268 (0.00%)  1/287 (0.35%) 
Disorientation  1  1/268 (0.37%)  0/287 (0.00%) 
Confusional state  1  0/268 (0.00%)  2/287 (0.70%) 
Mental status changes  1  3/268 (1.12%)  0/287 (0.00%) 
Psychotic disorder  1  1/268 (0.37%)  0/287 (0.00%) 
Panic attack  1  0/268 (0.00%)  1/287 (0.35%) 
Renal and urinary disorders     
Urinary retention  1  1/268 (0.37%)  2/287 (0.70%) 
Haematuria  1  0/268 (0.00%)  1/287 (0.35%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea at rest  1  0/268 (0.00%)  1/287 (0.35%) 
Pulmonary embolism  1  3/268 (1.12%)  11/287 (3.83%) 
Respiratory failure  1  4/268 (1.49%)  6/287 (2.09%) 
Chronic obstructive pulmonary disease  1  1/268 (0.37%)  2/287 (0.70%) 
Pleural effusion  1  3/268 (1.12%)  8/287 (2.79%) 
Pulmonary haemorrhage  1  0/268 (0.00%)  1/287 (0.35%) 
Hydrothorax  1  1/268 (0.37%)  0/287 (0.00%) 
Dyspnoea  1  5/268 (1.87%)  9/287 (3.14%) 
Haemoptysis  1  3/268 (1.12%)  2/287 (0.70%) 
Hypoxia  1  2/268 (0.75%)  2/287 (0.70%) 
Lung infiltration  1  0/268 (0.00%)  1/287 (0.35%) 
Interstitial lung disease  1  0/268 (0.00%)  2/287 (0.70%) 
Pneumonitis  1  0/268 (0.00%)  4/287 (1.39%) 
Acute respiratory failure  1  1/268 (0.37%)  0/287 (0.00%) 
Hiccups  1  1/268 (0.37%)  0/287 (0.00%) 
Vascular disorders     
Jugular vein thrombosis  1  1/268 (0.37%)  0/287 (0.00%) 
Femoral artery occlusion  1  0/268 (0.00%)  1/287 (0.35%) 
Peripheral artery stenosis  1  0/268 (0.00%)  1/287 (0.35%) 
Deep vein thrombosis  1  2/268 (0.75%)  1/287 (0.35%) 
Embolism  1  0/268 (0.00%)  1/287 (0.35%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DOCETAXEL NIVOLUMAB 3 mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   257/268 (95.90%)   257/287 (89.55%) 
Blood and lymphatic system disorders     
Anaemia  1  66/268 (24.63%)  32/287 (11.15%) 
Leukopenia  1  28/268 (10.45%)  0/287 (0.00%) 
Neutropenia  1  82/268 (30.60%)  2/287 (0.70%) 
Endocrine disorders     
Hypothyroidism  1  0/268 (0.00%)  19/287 (6.62%) 
Eye disorders     
Lacrimation increased  1  22/268 (8.21%)  3/287 (1.05%) 
Gastrointestinal disorders     
Constipation  1  45/268 (16.79%)  66/287 (23.00%) 
Abdominal pain  1  15/268 (5.60%)  14/287 (4.88%) 
Nausea  1  78/268 (29.10%)  63/287 (21.95%) 
Stomatitis  1  24/268 (8.96%)  5/287 (1.74%) 
Diarrhoea  1  72/268 (26.87%)  44/287 (15.33%) 
Vomiting  1  29/268 (10.82%)  36/287 (12.54%) 
General disorders     
Non-cardiac chest pain  1  14/268 (5.22%)  15/287 (5.23%) 
Pyrexia  1  40/268 (14.93%)  33/287 (11.50%) 
Pain  1  18/268 (6.72%)  20/287 (6.97%) 
Asthenia  1  60/268 (22.39%)  58/287 (20.21%) 
Fatigue  1  101/268 (37.69%)  91/287 (31.71%) 
Mucosal inflammation  1  20/268 (7.46%)  6/287 (2.09%) 
Oedema peripheral  1  45/268 (16.79%)  31/287 (10.80%) 
Infections and infestations     
Upper respiratory tract infection  1  12/268 (4.48%)  17/287 (5.92%) 
Investigations     
White blood cell count decreased  1  22/268 (8.21%)  0/287 (0.00%) 
Neutrophil count decreased  1  18/268 (6.72%)  1/287 (0.35%) 
Weight decreased  1  16/268 (5.97%)  22/287 (7.67%) 
Alanine aminotransferase increased  1  5/268 (1.87%)  16/287 (5.57%) 
Metabolism and nutrition disorders     
Decreased appetite  1  58/268 (21.64%)  83/287 (28.92%) 
Hyperglycaemia  1  15/268 (5.60%)  12/287 (4.18%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  26/268 (9.70%)  26/287 (9.06%) 
Arthralgia  1  32/268 (11.94%)  46/287 (16.03%) 
Musculoskeletal pain  1  12/268 (4.48%)  38/287 (13.24%) 
Myalgia  1  35/268 (13.06%)  18/287 (6.27%) 
Back pain  1  15/268 (5.60%)  35/287 (12.20%) 
Nervous system disorders     
Dysgeusia  1  27/268 (10.07%)  7/287 (2.44%) 
Paraesthesia  1  23/268 (8.58%)  12/287 (4.18%) 
Neuropathy peripheral  1  25/268 (9.33%)  9/287 (3.14%) 
Headache  1  32/268 (11.94%)  28/287 (9.76%) 
Dizziness  1  24/268 (8.96%)  25/287 (8.71%) 
Psychiatric disorders     
Insomnia  1  22/268 (8.21%)  20/287 (6.97%) 
Anxiety  1  5/268 (1.87%)  16/287 (5.57%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  62/268 (23.13%)  76/287 (26.48%) 
Oropharyngeal pain  1  15/268 (5.60%)  11/287 (3.83%) 
Dyspnoea  1  61/268 (22.76%)  60/287 (20.91%) 
Dyspnoea exertional  1  16/268 (5.97%)  8/287 (2.79%) 
Haemoptysis  1  15/268 (5.60%)  15/287 (5.23%) 
Productive cough  1  10/268 (3.73%)  15/287 (5.23%) 
Skin and subcutaneous tissue disorders     
Rash  1  13/268 (4.85%)  36/287 (12.54%) 
Pruritus  1  5/268 (1.87%)  33/287 (11.50%) 
Alopecia  1  70/268 (26.12%)  4/287 (1.39%) 
Erythema  1  18/268 (6.72%)  6/287 (2.09%) 
Dry skin  1  8/268 (2.99%)  20/287 (6.97%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01673867     History of Changes
Other Study ID Numbers: CA209-057
2012-002472-14 ( EudraCT Number )
First Submitted: August 24, 2012
First Posted: August 28, 2012
Results First Submitted: January 29, 2016
Results First Posted: February 26, 2016
Last Update Posted: April 10, 2018