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Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017)

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ClinicalTrials.gov Identifier: NCT01642004
Recruitment Status : Active, not recruiting
First Posted : July 17, 2012
Results First Posted : March 17, 2016
Last Update Posted : June 26, 2020
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 Squamous Cell Non-small Cell Lung Cancer
Interventions Biological: Nivolumab
Drug: Docetaxel
Enrollment 352
Recruitment Details  
Pre-assignment Details A total of 352 participants enrolled in the study; 272 were randomized to a treatment group. Of the 80 participants not randomized, 67 no longer met study criteria, 6 experienced an Adverse Event (AE), 3 withdrew consent, 3 died, and 1 failed screening. Study is ongoing.
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description Nivolumab 3 mg/kg solution intravenously 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 solution intravenously 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 135 137
Completed 131 129
Not Completed 4 8
Reason Not Completed
Adverse Event unrelated to study drug             1             0
Withdrawal by Subject             1             6
No longer meets study criteria             2             2
Period Title: Treatment
Started 131 129
Completed 21 2
Not Completed 110 127
Reason Not Completed
Disease progression             88             80
Study drug toxicity             5             13
Death             1             0
Adverse event unrelated to study drug             6             13
Withdrawal by Subject             5             9
Maximum clinical benefit             2             7
Poor/non-compliance             1             0
No longer meets study criteria             1             2
Other             1             2
Missing from data             0             1
Arm/Group Title Nivolumab Docetaxel Total
Hide Arm/Group Description Nivolumab 3 mg/kg solution intravenously 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 solution intravenously 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 135 137 272
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 135 participants 137 participants 272 participants
62.2  (8.33) 64.4  (8.28) 63.3  (8.36)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
<= 18 years 0 0 0
< 65 years 79 73 152
>= 65 AND < 75 years 45 46 91
>= 75 AND < 85 years 10 18 28
>= 85 years 1 0 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Female
24
  17.8%
40
  29.2%
64
  23.5%
Male
111
  82.2%
97
  70.8%
208
  76.5%
PD-L1 Expression Level  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
PD-L1 expression >= 5% 42 39 81
PD-L1 expression < 5% 75 69 144
PD-L1 not quantifiable at baseline 18 29 47
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 196 deaths, with the actual analysis occurring at 199 deaths.
Time Frame Randomization until 199 deaths, up to November 2014, approximately 25 months
Hide 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 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 solution intravenously 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 135 137
Median (95% Confidence Interval)
Unit of Measure: months
9.23
(7.33 to 13.27)
6.01
(5.13 to 7.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Stratified by region (US/Canada, Rest Of World (ROW), Europe) and prior treatment regimen (Paclitaxel, Another agent) as entered in the Interactive Voice Response System (IVRS).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.59
Confidence Interval (2-Sided) 96.85%
0.43 to 0.81
Estimation Comments Stratified Cox proportional hazard model. HR = Nivolumab over Docetaxel
2.Primary Outcome
Title Overall Survival (OS) Rate in All Randomized Participants
Hide Description The overall survival rate is the probability that a participant will be alive at 6, 12, and 18 months following randomization. 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 Randomization to 18 months post-randomization, up to June 2015
Hide 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 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 solution intravenously 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 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability of OS
6 months
63.7
(55.0 to 71.2)
50.7
(42.1 to 58.8)
12 months
42.2
(33.8 to 50.4)
24.3
(17.4 to 31.7)
18 months
28.1
(20.8 to 35.8)
12.5
(7.6 to 18.7)
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 196 deaths, with the actual analysis occurring at 199 deaths.
Time Frame Randomization until 199 deaths, up to November 2014, approximately 25 months
Hide 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 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 solution intravenously 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 135 137
Measure Type: Number
Unit of Measure: participants
86 113
4.Secondary Outcome
Title Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint
Hide Description

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). 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 199 deaths, up to November 2014, approximately 25 months
Hide 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 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 solution intravenously 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 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.0
(13.6 to 27.7)
8.8
(4.6 to 14.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by region (US/Canada vs Europe vs ROW) and prior treatment regimen (Paclitaxel vs Another Agent) as entered into the IVRS.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.64
Confidence Interval (2-Sided) 95%
1.27 to 5.49
Estimation Comments OR = Nivolumab over Docetaxel
5.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 November 2014, approximately 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
All confirmed responders (participants demonstrating CR or PR)
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously 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 solution intravenously 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 27 12
Median (Full Range)
Unit of Measure: months
2.23
(1.6 to 11.8)
2.09
(1.8 to 9.5)
6.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, up to November 2014, approximately 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
All confirmed responders (participants demonstrating CR or PR)
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously 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 solution intravenously 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 27 12
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(9.76 to NA)
8.41
(3.58 to 10.84)
[1]
Median DOR was not reached in the Nivolumab group
7.Secondary Outcome
Title Progression-Free Survival (PFS) at Primary Endpoint
Hide Description PFS rate was defined as the probability that participants will experience no disease progression or death from any cause at a given time point following randomization. Progression was assessed by investigators according to RECIST v1.1. 95% CIs were estimated using the Kaplan-Meier method. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative radiation therapy (RT) of non-target bone lesions or CNS lesions) without a prior reported progression were to be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy
Time Frame Randomization to 12 months post-randomization, up to November 2014
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (105 PFS events in Nivolumab arm; 122 PFS events in Docetaxel arm)
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously 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 solution intravenously 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 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability of PFS
6 months
38.4
(30.0 to 46.8)
21.9
(15.1 to 29.5)
12 months
20.8
(14.0 to 28.4)
6.4
(2.9 to 11.8)
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% CI for median PFS were computed by Brookmeyer and Crowley method (using log-log transformation). Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative RT of non-target bone lesions or CNS lesions) without a prior reported progression were to be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy.
Time Frame Randomization until 199 deaths, up to November 2014, approximately 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (105 PFS events in Nivolumab arm; 122 PFS events in Docetaxel arm)
Arm/Group Title Nivolumab Docetaxel
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution intravenously 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 solution intravenously 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 135 137
Median (95% Confidence Interval)
Unit of Measure: months
3.48
(2.14 to 4.86)
2.83
(2.10 to 3.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Log Rank
Comments Stratified by region (US/Canada vs Europe vs ROW) and prior treatment regimen (Paclitaxel vs Another Agent) as entered into the IVRS.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.47 to 0.81
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
Hide 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 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 solution intravenously 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 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.5
(12.4 to 26.1)
21.2
(14.7 to 29.0)
10.Secondary Outcome
Title Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint
Hide Description OS was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. 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. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
Time Frame Randomization until 199 deaths, up to November 2014, approximately 25 months
Hide 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 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 solution intravenously 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 135 137
Median (95% Confidence Interval)
Unit of Measure: months
PD-L1 expression >= 5% (n=42,39)
9.95
(5.82 to 17.15)
6.37
(4.50 to 9.03)
PD-L1 expression < 5% (n=50,55)
8.54
(5.49 to 13.27)
6.14
(5.13 to 8.28)
PD-L1 not quantifiable at baseline (n=18,29)
9.41 [1] 
(7.10 to NA)
5.06
(3.02 to 6.11)
[1]
Upper CI not reached
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression >= 5%
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.31 to 0.89
Estimation Comments HR = Nivolumab over Docetaxel; PD-L1 expression >= 5%
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression < 5%
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.47 to 1.02
Estimation Comments HR = Nivolumab over Docetaxel; PD-L1 expression < 5%
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 (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.19 to 0.82
Estimation Comments HR = Nivolumab over Docetaxel; PD-L1 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. 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). 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. 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 199 deaths, up to November 2014, approximately 25 months
Hide 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 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 solution intravenously 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 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
PD-L1 expression >= 5% (n=42,39)
21.4
(10.3 to 36.8)
7.7
(1.6 to 20.9)
PD-L1 expression < 5% (n=75,69)
14.7
(7.6 to 24.7)
11.6
(5.1 to 21.6)
PD-L1 not quantifiable at baseline (n=18,29)
38.9
(17.3 to 64.3)
3.4
(0.1 to 17.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression >= 5%
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
0.7 to 20.1
Estimation Comments OR = Nivolumab over Docetaxel; PD-L1 expression >= 5%
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 < 5%
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
0.4 to 4.0
Estimation Comments OR = Nivolumab over Docetaxel; PD-L1 expression < 5%
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 (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 17.8
Confidence Interval (2-Sided) 95%
1.8 to 830.7
Estimation Comments OR = Nivolumab over Docetaxel; PD-L1 expression not quantifiable at baseline
12.Secondary Outcome
Title Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint
Hide Description PFS time was measured for all randomized participants grouped by their baseline PD-L1 expression levels. 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. The PFS curves were estimated using KM method. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started subsequent anti-cancer therapy (including on-treatment palliative radiotherapy of non-target bone lesions or CNS lesions) without a prior reported progression were censored at the last evaluable tumor assessment prior to subsequent anti-cancer therapy. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
Time Frame Randomization until 199 deaths, up to November 2014, approximately 25 months
Hide 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 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 solution intravenously 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 135 137
Median (95% Confidence Interval)
Unit of Measure: months
PD-L1 expression >= 5% (n=42,39)
4.80
(2.10 to 7.56)
3.06
(1.94 to 4.63)
PD-L1 expression < 5% (n=75,69)
2.23
(1.94 to 4.73)
2.92
(2.10 to 3.55)
PD-L1 not quantifiable at baseline (n=18,29)
5.39
(2.10 to 10.45)
2.23
(2.04 to 4.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression >= 5%
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.32 to 0.90
Estimation Comments HR = Nivolumab over Docetaxel; PD-L1 expression >= 5%
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments PD-L1 expression < 5%
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.52 to 1.08
Estimation Comments HR = Nivolumab over Docetaxel; PD-L1 expression < 5%
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 (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.23 to 0.89
Estimation Comments HR = Nivolumab over Docetaxel; PD-L1 expression not quantifiable at baseline
13.Other Pre-specified Outcome
Title Overall Survival (OS) Time in Months for All Randomized Participants at Updated Survival Follow-up
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. Survival follow-up analysis occurred 7.4 months after Primary Endpoint was reached, representing a minimum OS follow-up time of 18.0 months.
Time Frame Randomization until July 2015, approximately 33 months
Hide 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 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 solution intravenously 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 135 137
Median (95% Confidence Interval)
Unit of Measure: months
9.23
(7.33 to 12.62)
6.01
(5.29 to 7.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments Stratified by region (US/Canada, Rest Of World (ROW), Europe) and prior treatment regimen (Paclitaxel, Another agent) as entered in the Interactive Voice Response System (IVRS).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.47 to 0.81
Estimation Comments Hazard Ratio (HR) = Nivolumab over Docetaxel
Time Frame From first dose to last dose plus 30 days up to Primary Endpoint (November 2014)
Adverse Event Reporting Description Study initiated: October 2012; Primary Endpoint: November 2014
 
Arm/Group Title NIVOLUMAB DOCETAXEL
Hide Arm/Group Description Nivolumab 3 mg/kg solution intravenously 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 solution intravenously 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.
All-Cause Mortality
NIVOLUMAB DOCETAXEL
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
NIVOLUMAB DOCETAXEL
Affected / at Risk (%) Affected / at Risk (%)
Total   61/131 (46.56%)   70/129 (54.26%) 
Blood and lymphatic system disorders     
Anaemia  1  2/131 (1.53%)  0/129 (0.00%) 
Febrile neutropenia  1  0/131 (0.00%)  13/129 (10.08%) 
Neutropenia  1  1/131 (0.76%)  4/129 (3.10%) 
Febrile bone marrow aplasia  1  0/131 (0.00%)  1/129 (0.78%) 
Pancytopenia  1  0/131 (0.00%)  1/129 (0.78%) 
Cardiac disorders     
Cardiac tamponade  1  1/131 (0.76%)  1/129 (0.78%) 
Sinus bradycardia  1  1/131 (0.76%)  0/129 (0.00%) 
Cardio-respiratory arrest  1  1/131 (0.76%)  1/129 (0.78%) 
Atrial thrombosis  1  1/131 (0.76%)  0/129 (0.00%) 
Atrial fibrillation  1  0/131 (0.00%)  3/129 (2.33%) 
Endocrine disorders     
Hypothyroidism  1  1/131 (0.76%)  0/129 (0.00%) 
Goitre  1  0/131 (0.00%)  1/129 (0.78%) 
Gastrointestinal disorders     
Vomiting  1  0/131 (0.00%)  1/129 (0.78%) 
Diarrhoea  1  0/131 (0.00%)  1/129 (0.78%) 
Intestinal perforation  1  0/131 (0.00%)  1/129 (0.78%) 
Nausea  1  0/131 (0.00%)  1/129 (0.78%) 
Abdominal pain  1  0/131 (0.00%)  1/129 (0.78%) 
Dysphagia  1  2/131 (1.53%)  0/129 (0.00%) 
Constipation  1  0/131 (0.00%)  1/129 (0.78%) 
General disorders     
Pyrexia  1  5/131 (3.82%)  1/129 (0.78%) 
Chills  1  1/131 (0.76%)  0/129 (0.00%) 
Asthenia  1  0/131 (0.00%)  2/129 (1.55%) 
General physical health deterioration  1  1/131 (0.76%)  0/129 (0.00%) 
Sudden death  1  1/131 (0.76%)  0/129 (0.00%) 
Infections and infestations     
Enterocolitis infectious  1  0/131 (0.00%)  1/129 (0.78%) 
Infection  1  1/131 (0.76%)  2/129 (1.55%) 
Skin infection  1  0/131 (0.00%)  1/129 (0.78%) 
Pneumonia  1  7/131 (5.34%)  10/129 (7.75%) 
Lung infection  1  0/131 (0.00%)  3/129 (2.33%) 
Upper respiratory tract infection  1  2/131 (1.53%)  0/129 (0.00%) 
Lower respiratory tract infection  1  1/131 (0.76%)  0/129 (0.00%) 
Neutropenic infection  1  0/131 (0.00%)  1/129 (0.78%) 
Bronchitis  1  1/131 (0.76%)  1/129 (0.78%) 
Septic shock  1  0/131 (0.00%)  1/129 (0.78%) 
Bronchopneumonia  1  0/131 (0.00%)  1/129 (0.78%) 
Clostridium difficile colitis  1  0/131 (0.00%)  1/129 (0.78%) 
Lobar pneumonia  1  1/131 (0.76%)  0/129 (0.00%) 
Respiratory tract infection  1  1/131 (0.76%)  1/129 (0.78%) 
Sepsis  1  0/131 (0.00%)  2/129 (1.55%) 
Urinary tract infection  1  1/131 (0.76%)  1/129 (0.78%) 
Investigations     
C-reactive protein increased  1  1/131 (0.76%)  0/129 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  2/131 (1.53%)  3/129 (2.33%) 
Hypercalcaemia  1  4/131 (3.05%)  0/129 (0.00%) 
Hyponatraemia  1  0/131 (0.00%)  1/129 (0.78%) 
Hypoglycaemia  1  0/131 (0.00%)  1/129 (0.78%) 
Hypophosphataemia  1  1/131 (0.76%)  0/129 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/131 (0.76%)  0/129 (0.00%) 
Musculoskeletal pain  1  0/131 (0.00%)  1/129 (0.78%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain  1  0/131 (0.00%)  1/129 (0.78%) 
Malignant neoplasm progression  1  18/131 (13.74%)  9/129 (6.98%) 
Metastases to central nervous system  1  0/131 (0.00%)  1/129 (0.78%) 
Nervous system disorders     
Generalised tonic-clonic seizure  1  1/131 (0.76%)  0/129 (0.00%) 
Cerebrovascular accident  1  0/131 (0.00%)  2/129 (1.55%) 
Ischaemic stroke  1  1/131 (0.76%)  0/129 (0.00%) 
Aphasia  1  0/131 (0.00%)  1/129 (0.78%) 
Myasthenic syndrome  1  1/131 (0.76%)  0/129 (0.00%) 
Convulsion  1  1/131 (0.76%)  0/129 (0.00%) 
Peripheral sensory neuropathy  1  0/131 (0.00%)  1/129 (0.78%) 
Spinal cord compression  1  1/131 (0.76%)  0/129 (0.00%) 
VIIth nerve paralysis  1  0/131 (0.00%)  1/129 (0.78%) 
Psychiatric disorders     
Mental status changes  1  0/131 (0.00%)  1/129 (0.78%) 
Delirium  1  0/131 (0.00%)  1/129 (0.78%) 
Confusional state  1  0/131 (0.00%)  1/129 (0.78%) 
Renal and urinary disorders     
Calculus ureteric  1  0/131 (0.00%)  1/129 (0.78%) 
Tubulointerstitial nephritis  1  1/131 (0.76%)  0/129 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  0/131 (0.00%)  1/129 (0.78%) 
Pneumothorax  1  0/131 (0.00%)  1/129 (0.78%) 
Dyspnoea  1  2/131 (1.53%)  2/129 (1.55%) 
Haemoptysis  1  1/131 (0.76%)  2/129 (1.55%) 
Cough  1  1/131 (0.76%)  0/129 (0.00%) 
Pneumonitis  1  2/131 (1.53%)  0/129 (0.00%) 
Pulmonary haemorrhage  1  0/131 (0.00%)  3/129 (2.33%) 
Acute respiratory failure  1  0/131 (0.00%)  1/129 (0.78%) 
Chronic obstructive pulmonary disease  1  2/131 (1.53%)  1/129 (0.78%) 
Pleural effusion  1  0/131 (0.00%)  1/129 (0.78%) 
Pulmonary thrombosis  1  1/131 (0.76%)  0/129 (0.00%) 
Stridor  1  0/131 (0.00%)  1/129 (0.78%) 
Interstitial lung disease  1  0/131 (0.00%)  1/129 (0.78%) 
Respiratory failure  1  2/131 (1.53%)  2/129 (1.55%) 
Pulmonary embolism  1  2/131 (1.53%)  2/129 (1.55%) 
Vascular disorders     
Arterial haemorrhage  1  0/131 (0.00%)  1/129 (0.78%) 
Peripheral ischaemia  1  1/131 (0.76%)  0/129 (0.00%) 
Superior vena cava syndrome  1  0/131 (0.00%)  1/129 (0.78%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
NIVOLUMAB DOCETAXEL
Affected / at Risk (%) Affected / at Risk (%)
Total   114/131 (87.02%)   119/129 (92.25%) 
Blood and lymphatic system disorders     
Anaemia  1  22/131 (16.79%)  37/129 (28.68%) 
Leukopenia  1  1/131 (0.76%)  9/129 (6.98%) 
Neutropenia  1  1/131 (0.76%)  41/129 (31.78%) 
Gastrointestinal disorders     
Vomiting  1  10/131 (7.63%)  17/129 (13.18%) 
Diarrhoea  1  20/131 (15.27%)  33/129 (25.58%) 
Nausea  1  20/131 (15.27%)  32/129 (24.81%) 
Abdominal pain  1  7/131 (5.34%)  9/129 (6.98%) 
Constipation  1  17/131 (12.98%)  19/129 (14.73%) 
General disorders     
Pyrexia  1  20/131 (15.27%)  24/129 (18.60%) 
Chest pain  1  10/131 (7.63%)  12/129 (9.30%) 
Chills  1  7/131 (5.34%)  1/129 (0.78%) 
Mucosal inflammation  1  3/131 (2.29%)  13/129 (10.08%) 
Fatigue  1  40/131 (30.53%)  51/129 (39.53%) 
Asthenia  1  20/131 (15.27%)  27/129 (20.93%) 
Oedema peripheral  1  10/131 (7.63%)  16/129 (12.40%) 
Infections and infestations     
Upper respiratory tract infection  1  7/131 (5.34%)  4/129 (3.10%) 
Bronchitis  1  12/131 (9.16%)  4/129 (3.10%) 
Investigations     
Neutrophil count decreased  1  0/131 (0.00%)  8/129 (6.20%) 
Weight decreased  1  12/131 (9.16%)  6/129 (4.65%) 
White blood cell count decreased  1  0/131 (0.00%)  8/129 (6.20%) 
Metabolism and nutrition disorders     
Hypercalcaemia  1  8/131 (6.11%)  0/129 (0.00%) 
Hypomagnesaemia  1  7/131 (5.34%)  4/129 (3.10%) 
Decreased appetite  1  32/131 (24.43%)  35/129 (27.13%) 
Hyperglycaemia  1  9/131 (6.87%)  10/129 (7.75%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  2/131 (1.53%)  7/129 (5.43%) 
Musculoskeletal chest pain  1  7/131 (5.34%)  3/129 (2.33%) 
Myalgia  1  3/131 (2.29%)  15/129 (11.63%) 
Back pain  1  12/131 (9.16%)  11/129 (8.53%) 
Arthralgia  1  13/131 (9.92%)  16/129 (12.40%) 
Musculoskeletal pain  1  8/131 (6.11%)  7/129 (5.43%) 
Nervous system disorders     
Paraesthesia  1  4/131 (3.05%)  8/129 (6.20%) 
Headache  1  18/131 (13.74%)  9/129 (6.98%) 
Dizziness  1  11/131 (8.40%)  12/129 (9.30%) 
Neuropathy peripheral  1  4/131 (3.05%)  15/129 (11.63%) 
Psychiatric disorders     
Insomnia  1  7/131 (5.34%)  6/129 (4.65%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  46/131 (35.11%)  38/129 (29.46%) 
Haemoptysis  1  8/131 (6.11%)  9/129 (6.98%) 
Cough  1  40/131 (30.53%)  24/129 (18.60%) 
Dysphonia  1  9/131 (6.87%)  1/129 (0.78%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  10/131 (7.63%)  3/129 (2.33%) 
Rash  1  10/131 (7.63%)  11/129 (8.53%) 
Alopecia  1  1/131 (0.76%)  29/129 (22.48%) 
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
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01642004    
Other Study ID Numbers: CA209-017
2011-004792-36 ( EudraCT Number )
First Submitted: July 9, 2012
First Posted: July 17, 2012
Results First Submitted: February 19, 2016
Results First Posted: March 17, 2016
Last Update Posted: June 26, 2020