Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017)
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01642004
Collaborator
(none)
352
106
2
106
3.3
0
Study Details
Study Description
Brief Summary
The purpose of the study is to compare the overall survival of BMS-936558 as compared with Docetaxel in subjects with squamous cell non-small cell lung cancer (NSCLC), after failure of prior platinum-based chemotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
352 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC)
Actual Study Start Date
:
Oct 16, 2012
Actual Primary Completion Date
:
Nov 17, 2014
Actual Study Completion Date
:
Aug 16, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A: Nivolumab 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. |
Biological: Nivolumab
Other Names:
|
| Experimental: Arm B: Docetaxel Docetaxel 75 mg/m^2 concentrate for solution for intravenous 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. |
Drug: Docetaxel
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint [Randomization until 199 deaths, up to November 2014, approximately 25 months]
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.
- Overall Survival (OS) Rate in All Randomized Participants [Randomization to 18 months post-randomization, up to June 2015]
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.
- Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint [Randomization until 199 deaths, up to November 2014, approximately 25 months]
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.
Secondary Outcome Measures
- Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint [Randomization until 199 deaths, up to November 2014, approximately 25 months]
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 To Response (TTR) in Months for All Confirmed Responders at Primary Endpoint [Randomization until confirmed response, up to November 2014, approximately 25 months]
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.
- Duration of Objective Response (DOR) in Months for All Confirmed Responders at Primary Endpoint [Date of confirmed response to date of documented tumor progression, up to November 2014, approximately 25 months]
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.
- Progression-Free Survival (PFS) at Primary Endpoint [Randomization to 12 months post-randomization, up to November 2014]
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
- Progression-Free Survival (PFS) Time in Months for All Randomized Participants at Primary Endpoint [Randomization until 199 deaths, up to November 2014, approximately 25 months]
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.
- Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12 [Randomization to Week 12]
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.
- Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint [Randomization until 199 deaths, up to November 2014, approximately 25 months]
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.
- Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint [Randomization until 199 deaths, up to November 2014, approximately 25 months]
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.
- Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint [Randomization until 199 deaths, up to November 2014, approximately 25 months]
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.
Other Outcome Measures
- Overall Survival (OS) Time in Months for All Randomized Participants at Updated Survival Follow-up [Randomization until July 2015, approximately 33 months]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Men and women ≥18 years of age
-
Subjects with histologically or cytologically-documented squamous cell NSCLC who present with Stage IIIB/IV disease or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiation therapy for locally advanced disease)
-
Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
-
Measurable disease by computed tomography (CT)/Magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
-
A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient
Exclusion Criteria:
-
Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent)
-
Subjects with carcinomatous meningitis
-
Subjects with active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
-
Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
-
Prior therapy with anti-Programmed death-1 (PD-1), anti-Programmed cell death ligand 1 (PD-L1), anti-Programmed cell death ligand 2 (PD-L2), anti-CD137, or anti-Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
-
Prior treatment on the first line study CA184104 first line NSCLC study
-
Prior treatment with Docetaxel
-
Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
-
Treatment with any investigational agent within 14 days of first administration of study treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Arizona | Scottsdale | Arizona | United States | 85259 |
| 2 | City Of Hope | Duarte | California | United States | 91010-3000 |
| 3 | Yale University | New Haven | Connecticut | United States | 06520 |
| 4 | H. Lee Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
| 5 | Northwest Georgia Oncology Ctr | Marietta | Georgia | United States | 30060 |
| 6 | University Of Chicago Medical Center | Chicago | Illinois | United States | 60637 |
| 7 | Johns Hopkins Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | United States | 21287 |
| 8 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 9 | Winthrop University Hospital | Mineola | New York | United States | 11501 |
| 10 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 11 | Memorial Sloan Kettering Nassau | New York | New York | United States | 10065 |
| 12 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 13 | Oncology Hematology Care, Inc. | Cincinnati | Ohio | United States | 45242 |
| 14 | St Mary Medical Center | Langhorne | Pennsylvania | United States | 19047 |
| 15 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 16 | Guthrie Medical Group, P.C. | Sayre | Pennsylvania | United States | 18840 |
| 17 | South Carolina Oncology Associates | Columbia | South Carolina | United States | 29210 |
| 18 | Chattanooga Oncology Hematology Associates | Chattanooga | Tennessee | United States | 37404 |
| 19 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37203 |
| 20 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 21 | University Of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 22 | The University Of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 23 | Swedish Cancer Institute | Seattle | Washington | United States | 98104 |
| 24 | University of Washington - Seattle Cancer Care Alliance | Seattle | Washington | United States | 98109 |
| 25 | West Virginia University-Mbrcc | Morgantown | West Virginia | United States | 26506-9162 |
| 26 | Local Institution | Capital Federal | Buenos Aires | Argentina | 1431 |
| 27 | Local Institution | Ciudad Autónoma De Buenos Aire | Buenos Aires | Argentina | CP1426ANZ |
| 28 | Local Institution | San Miguel De Tucuman | Tucuman | Argentina | CPT4000IAK |
| 29 | Local Institution | Buenos Aires | Argentina | C1280AEB | |
| 30 | Local Institution | Cordoba | Argentina | X5002AOQ | |
| 31 | Local Institution | Wollongong | New South Wales | Australia | 2500 |
| 32 | Local Institution | Adelaide | South Australia | Australia | 5000 |
| 33 | Local Institution | Elizabeth Vale | South Australia | Australia | 5112 |
| 34 | Local Institution | Kurralta Park | South Australia | Australia | 5037 |
| 35 | Local Institution | Clayton | Victoria | Australia | 3168 |
| 36 | Local Institution | Linz | Austria | 4020 | |
| 37 | Local Institution | Salzburg | Austria | 5020 | |
| 38 | Local Institution | Vienna | Austria | 1130 | |
| 39 | Local Institution | Wels | Austria | 4600 | |
| 40 | Cancercare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 41 | Jewish General Hospital | Montreal | Quebec | Canada | H3T 1E2 |
| 42 | CISSS du Bas-Saint-Laurent Hopital Regional de Rimouski | Rimouski | Quebec | Canada | G5L 5T1 |
| 43 | Local Institution | Santiago | Metropolitana | Chile | 7600448 |
| 44 | Local Institution | Recoleta | Santiago De Chile | Chile | |
| 45 | Local Institution | Viña Del Mar | Valparaiso | Chile | |
| 46 | Local Institution | Antofagasta | Chile | 240000 | |
| 47 | Local Institution | Santiago | Chile | 7630370 | |
| 48 | Local Institution | Praha 8 | Czechia | 180 81 | |
| 49 | Local Institution | Avignon Cedes 9 | France | 84918 | |
| 50 | Local Institution | Caen | France | 14000 | |
| 51 | Local Institution | Dijon | France | 21000 | |
| 52 | Local Institution | La Roche Sur Yon Cedex 9 | France | 85925 | |
| 53 | Local Institution | Lyon Cedex 08 | France | 69373 | |
| 54 | Local Institution | Marseille Cedex 20 | France | 13915 | |
| 55 | Local Institution | Pierre Benite | France | 69495 | |
| 56 | Local Institution | Rennes Cedex 9 | France | 35033 | |
| 57 | Local Institution | Strasbourg | France | 67090 | |
| 58 | Local Institution | Toulouse | France | 31300 | |
| 59 | Local Institution | Bad Berka | Germany | 99437 | |
| 60 | Local Institution | Essen | Germany | 45122 | |
| 61 | Local Institution | Gerlingen | Germany | 70839 | |
| 62 | Local Institution | Grosshansdorf | Germany | 22927 | |
| 63 | Local Institution | Heidelberg | Germany | 69126 | |
| 64 | Local Institution | Koeln | Germany | 51109 | |
| 65 | Local Institution | Krefeld | Germany | 47805 | |
| 66 | Local Institution | Budapest | Hungary | H-1121 | |
| 67 | Local Institution | Dublin 8 | Dublin | Ireland | |
| 68 | Local Institution | Dublin 9 | Dublin | Ireland | |
| 69 | Local Institution | Bologna | Italy | 40138 | |
| 70 | Local Institution | Meldola (fc) | Italy | 47014 | |
| 71 | Local Institution | Milano | Italy | 20133 | |
| 72 | Local Institution | Padova | Italy | 35128 | |
| 73 | Local Institution | Perugia | Italy | 06132 | |
| 74 | Local Institution | Ravenna | Italy | 48100 | |
| 75 | Local Institution | Siena | Italy | 53100 | |
| 76 | Local Institution | Mexico | Distrito Federal | Mexico | 06735 |
| 77 | Local Institution | Mexico | Distrito Federal | Mexico | 14080 |
| 78 | Local Institution | Leon, Guanajato | Guanajuato | Mexico | 37000 |
| 79 | Local Institution | Hermosillo | Sonora | Mexico | 83280 |
| 80 | Local Institution | Amsterdam | Netherlands | 1066 CX | |
| 81 | Local Institution | Rotterdam | Netherlands | 3015 CE | |
| 82 | Local Institution | Oslo | Norway | 0310 | |
| 83 | Local Institution | Arequipa | Peru | 54 | |
| 84 | Local Institution | Lima | Peru | 34 | |
| 85 | Local Institution | Gdansk | Poland | 80-952 | |
| 86 | Local Institution | Krakow | Poland | 31-202 | |
| 87 | Local Institution | Olsztyn | Poland | 10-513 | |
| 88 | Local Institution | Szczecin | Poland | 70-891 | |
| 89 | Local Institution | Warszawa | Poland | 02-781 | |
| 90 | Local Institution | Bucuresti | Romania | 010976 | |
| 91 | Local Institution | Cluj-Napoca | Romania | 400352 | |
| 92 | Local Institution | Constanta | Romania | 900591 | |
| 93 | Local Institution | Craiova | Romania | 200385 | |
| 94 | Local Institution | Iasi | Romania | 700106 | |
| 95 | Local Institution | Timisoara | Romania | 300167 | |
| 96 | Local Institution | Moscow | Russian Federation | 115 478 | |
| 97 | Local Institution | St. Petersburg | Russian Federation | 198255 | |
| 98 | Local Institution | Barakaldo | Vizcaya | Spain | 48903 |
| 99 | Local Institution | Barcelona | Spain | 08035 | |
| 100 | Local Institution | Madrid | Spain | 28040 | |
| 101 | Local Institution | Madrid | Spain | 28050 | |
| 102 | Local Institution | Sevilla | Spain | 41013 | |
| 103 | Local Institution | Cottingham | East Yorkshire | United Kingdom | HU16 5JQ |
| 104 | Local Institution | Southampton | Hampshire | United Kingdom | SO16 6YD |
| 105 | Local Institution | Withington | Manchester | United Kingdom | M20 4BX |
| 106 | Local Institution | Sheffield | Yorkshire | United Kingdom | S10 2SJ |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- BMS Clinical Trial Information
- BMS Clinical Trial Patient Recruiting
- Investigator Inquiry Form
- FDA Safety Alerts and Recalls
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01642004
Other Study ID Numbers:
- CA209-017
- 2011-004792-36
First Posted:
Jul 17, 2012
Last Update Posted:
Feb 7, 2022
Last Verified:
Jan 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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 |
|---|---|---|
| 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 |
| Period Title: Randomization | ||
| STARTED | 131 | 129 |
| COMPLETED | 21 | 2 |
| NOT COMPLETED | 110 | 127 |
Baseline Characteristics
| Arm/Group Title | Nivolumab | Docetaxel | Total |
|---|---|---|---|
| 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 Participants | 135 | 137 | 272 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
62.2
(8.33)
|
64.4
(8.28)
|
63.3
(8.36)
|
| Age, Customized (participants) [Number] | |||
| <= 18 years |
0
0%
|
0
0%
|
0
0%
|
| < 65 years |
79
58.5%
|
73
53.3%
|
152
55.9%
|
| >= 65 AND < 75 years |
45
33.3%
|
46
33.6%
|
91
33.5%
|
| >= 75 AND < 85 years |
10
7.4%
|
18
13.1%
|
28
10.3%
|
| >= 85 years |
1
0.7%
|
0
0%
|
1
0.4%
|
| Sex: Female, Male (Count of 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 (participants) [Number] | |||
| PD-L1 expression >= 5% |
42
31.1%
|
39
28.5%
|
81
29.8%
|
| PD-L1 expression < 5% |
75
55.6%
|
69
50.4%
|
144
52.9%
|
| PD-L1 not quantifiable at baseline |
18
13.3%
|
29
21.2%
|
47
17.3%
|
Outcome Measures
| Title | Overall Survival (OS) Time in Months for All Randomized Participants at Updated Survival Follow-up |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| Median (95% Confidence Interval) [months] |
9.23
|
6.01
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Nivolumab, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| 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 | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.62 | |
| Confidence Interval |
(2-Sided) 95% 0.47 to 0.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard Ratio (HR) = Nivolumab over Docetaxel | |
| Title | Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| Number (95% Confidence Interval) [percentage of participants] |
20.0
14.8%
|
8.8
6.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Nivolumab, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0083 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | OR = Nivolumab over Docetaxel | |
| Title | Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| Median (95% Confidence Interval) [months] |
9.23
|
6.01
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Nivolumab, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| 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 | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.59 | |
| Confidence Interval |
(2-Sided) 96.85% 0.43 to 0.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazard model. HR = Nivolumab over Docetaxel | |
| Title | Overall Survival (OS) Rate in All Randomized Participants |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| 6 months |
63.7
|
50.7
|
| 12 months |
42.2
|
24.3
|
| 18 months |
28.1
|
12.5
|
| Title | Time To Response (TTR) in Months for All Confirmed Responders at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All confirmed responders (participants demonstrating CR or PR) |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 27 | 12 |
| Median (Full Range) [months] |
2.23
|
2.09
|
| Title | Duration of Objective Response (DOR) in Months for All Confirmed Responders at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All confirmed responders (participants demonstrating CR or PR) |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 27 | 12 |
| Median (95% Confidence Interval) [months] |
NA
|
8.41
|
| Title | Progression-Free Survival (PFS) at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants (105 PFS events in Nivolumab arm; 122 PFS events in Docetaxel arm) |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| 6 months |
38.4
|
21.9
|
| 12 months |
20.8
|
6.4
|
| Title | Progression-Free Survival (PFS) Time in Months for All Randomized Participants at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants (105 PFS events in Nivolumab arm; 122 PFS events in Docetaxel arm) |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| Median (95% Confidence Interval) [months] |
3.48
|
2.83
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Nivolumab, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR = Nivolumab over Docetaxel | |
| Title | Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| Number (95% Confidence Interval) [percentage of participants] |
18.5
13.7%
|
21.2
15.5%
|
| Title | Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| PD-L1 expression >= 5% (n=42,39) |
9.95
|
6.37
|
| PD-L1 expression < 5% (n=50,55) |
8.54
|
6.14
|
| PD-L1 not quantifiable at baseline (n=18,29) |
9.41
|
5.06
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.53 | |
| Confidence Interval |
(2-Sided) 95% 0.31 to 0.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR = Nivolumab over Docetaxel; PD-L1 expression >= 5% | |
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.70 | |
| Confidence Interval |
(2-Sided) 95% 0.47 to 1.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR = Nivolumab over Docetaxel; PD-L1 expression < 5% | |
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.39 | |
| Confidence Interval |
(2-Sided) 95% 0.19 to 0.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR = Nivolumab over Docetaxel; PD-L1 not quantifiable at baseline | |
| Title | Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| PD-L1 expression >= 5% (n=42,39) |
21.4
15.9%
|
7.7
5.6%
|
| PD-L1 expression < 5% (n=75,69) |
14.7
10.9%
|
11.6
8.5%
|
| PD-L1 not quantifiable at baseline (n=18,29) |
38.9
28.8%
|
3.4
2.5%
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 3.3 | |
| Confidence Interval |
(2-Sided) 95% 0.7 to 20.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | OR = Nivolumab over Docetaxel; PD-L1 expression >= 5% | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Nivolumab, Docetaxel |
|---|---|---|
| Comments | PD-L1 < 5% | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 95% 0.4 to 4.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | OR = Nivolumab over Docetaxel; PD-L1 expression < 5% | |
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 17.8 | |
| Confidence Interval |
(2-Sided) 95% 1.8 to 830.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | OR = Nivolumab over Docetaxel; PD-L1 expression not quantifiable at baseline | |
| Title | Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| PD-L1 expression >= 5% (n=42,39) |
4.80
|
3.06
|
| PD-L1 expression < 5% (n=75,69) |
2.23
|
2.92
|
| PD-L1 not quantifiable at baseline (n=18,29) |
5.39
|
2.23
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.54 | |
| Confidence Interval |
(2-Sided) 95% 0.32 to 0.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR = Nivolumab over Docetaxel; PD-L1 expression >= 5% | |
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 95% 0.52 to 1.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR = Nivolumab over Docetaxel; PD-L1 expression < 5% | |
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.45 | |
| Confidence Interval |
(2-Sided) 95% 0.23 to 0.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR = Nivolumab over Docetaxel; PD-L1 expression not quantifiable at baseline | |
| Title | Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Nivolumab | Docetaxel |
|---|---|---|
| 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. |
| Measure Participants | 135 | 137 |
| Number [participants] |
86
63.7%
|
113
82.5%
|
Adverse Events
| 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 | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| NIVOLUMAB | DOCETAXEL | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 61/131 (46.6%) | 70/129 (54.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/131 (1.5%) | 0/129 (0%) | ||
| Febrile neutropenia | 0/131 (0%) | 13/129 (10.1%) | ||
| Neutropenia | 1/131 (0.8%) | 4/129 (3.1%) | ||
| Febrile bone marrow aplasia | 0/131 (0%) | 1/129 (0.8%) | ||
| Pancytopenia | 0/131 (0%) | 1/129 (0.8%) | ||
| Cardiac disorders | ||||
| Cardiac tamponade | 1/131 (0.8%) | 1/129 (0.8%) | ||
| Sinus bradycardia | 1/131 (0.8%) | 0/129 (0%) | ||
| Cardio-respiratory arrest | 1/131 (0.8%) | 1/129 (0.8%) | ||
| Atrial thrombosis | 1/131 (0.8%) | 0/129 (0%) | ||
| Atrial fibrillation | 0/131 (0%) | 3/129 (2.3%) | ||
| Endocrine disorders | ||||
| Hypothyroidism | 1/131 (0.8%) | 0/129 (0%) | ||
| Goitre | 0/131 (0%) | 1/129 (0.8%) | ||
| Gastrointestinal disorders | ||||
| Vomiting | 0/131 (0%) | 1/129 (0.8%) | ||
| Diarrhoea | 0/131 (0%) | 1/129 (0.8%) | ||
| Intestinal perforation | 0/131 (0%) | 1/129 (0.8%) | ||
| Nausea | 0/131 (0%) | 1/129 (0.8%) | ||
| Abdominal pain | 0/131 (0%) | 1/129 (0.8%) | ||
| Dysphagia | 2/131 (1.5%) | 0/129 (0%) | ||
| Constipation | 0/131 (0%) | 1/129 (0.8%) | ||
| General disorders | ||||
| Pyrexia | 5/131 (3.8%) | 1/129 (0.8%) | ||
| Chills | 1/131 (0.8%) | 0/129 (0%) | ||
| Asthenia | 0/131 (0%) | 2/129 (1.6%) | ||
| General physical health deterioration | 1/131 (0.8%) | 0/129 (0%) | ||
| Sudden death | 1/131 (0.8%) | 0/129 (0%) | ||
| Infections and infestations | ||||
| Enterocolitis infectious | 0/131 (0%) | 1/129 (0.8%) | ||
| Infection | 1/131 (0.8%) | 2/129 (1.6%) | ||
| Skin infection | 0/131 (0%) | 1/129 (0.8%) | ||
| Pneumonia | 7/131 (5.3%) | 10/129 (7.8%) | ||
| Lung infection | 0/131 (0%) | 3/129 (2.3%) | ||
| Upper respiratory tract infection | 2/131 (1.5%) | 0/129 (0%) | ||
| Lower respiratory tract infection | 1/131 (0.8%) | 0/129 (0%) | ||
| Neutropenic infection | 0/131 (0%) | 1/129 (0.8%) | ||
| Bronchitis | 1/131 (0.8%) | 1/129 (0.8%) | ||
| Septic shock | 0/131 (0%) | 1/129 (0.8%) | ||
| Bronchopneumonia | 0/131 (0%) | 1/129 (0.8%) | ||
| Clostridium difficile colitis | 0/131 (0%) | 1/129 (0.8%) | ||
| Lobar pneumonia | 1/131 (0.8%) | 0/129 (0%) | ||
| Respiratory tract infection | 1/131 (0.8%) | 1/129 (0.8%) | ||
| Sepsis | 0/131 (0%) | 2/129 (1.6%) | ||
| Urinary tract infection | 1/131 (0.8%) | 1/129 (0.8%) | ||
| Investigations | ||||
| C-reactive protein increased | 1/131 (0.8%) | 0/129 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 2/131 (1.5%) | 3/129 (2.3%) | ||
| Hypercalcaemia | 4/131 (3.1%) | 0/129 (0%) | ||
| Hyponatraemia | 0/131 (0%) | 1/129 (0.8%) | ||
| Hypoglycaemia | 0/131 (0%) | 1/129 (0.8%) | ||
| Hypophosphataemia | 1/131 (0.8%) | 0/129 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/131 (0.8%) | 0/129 (0%) | ||
| Musculoskeletal pain | 0/131 (0%) | 1/129 (0.8%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumour pain | 0/131 (0%) | 1/129 (0.8%) | ||
| Malignant neoplasm progression | 18/131 (13.7%) | 9/129 (7%) | ||
| Metastases to central nervous system | 0/131 (0%) | 1/129 (0.8%) | ||
| Nervous system disorders | ||||
| Generalised tonic-clonic seizure | 1/131 (0.8%) | 0/129 (0%) | ||
| Cerebrovascular accident | 0/131 (0%) | 2/129 (1.6%) | ||
| Ischaemic stroke | 1/131 (0.8%) | 0/129 (0%) | ||
| Aphasia | 0/131 (0%) | 1/129 (0.8%) | ||
| Myasthenic syndrome | 1/131 (0.8%) | 0/129 (0%) | ||
| Convulsion | 1/131 (0.8%) | 0/129 (0%) | ||
| Peripheral sensory neuropathy | 0/131 (0%) | 1/129 (0.8%) | ||
| Spinal cord compression | 1/131 (0.8%) | 0/129 (0%) | ||
| VIIth nerve paralysis | 0/131 (0%) | 1/129 (0.8%) | ||
| Psychiatric disorders | ||||
| Mental status changes | 0/131 (0%) | 1/129 (0.8%) | ||
| Delirium | 0/131 (0%) | 1/129 (0.8%) | ||
| Confusional state | 0/131 (0%) | 1/129 (0.8%) | ||
| Renal and urinary disorders | ||||
| Calculus ureteric | 0/131 (0%) | 1/129 (0.8%) | ||
| Tubulointerstitial nephritis | 1/131 (0.8%) | 0/129 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Oropharyngeal pain | 0/131 (0%) | 1/129 (0.8%) | ||
| Pneumothorax | 0/131 (0%) | 1/129 (0.8%) | ||
| Dyspnoea | 2/131 (1.5%) | 2/129 (1.6%) | ||
| Haemoptysis | 1/131 (0.8%) | 2/129 (1.6%) | ||
| Cough | 1/131 (0.8%) | 0/129 (0%) | ||
| Pneumonitis | 2/131 (1.5%) | 0/129 (0%) | ||
| Pulmonary haemorrhage | 0/131 (0%) | 3/129 (2.3%) | ||
| Acute respiratory failure | 0/131 (0%) | 1/129 (0.8%) | ||
| Chronic obstructive pulmonary disease | 2/131 (1.5%) | 1/129 (0.8%) | ||
| Pleural effusion | 0/131 (0%) | 1/129 (0.8%) | ||
| Pulmonary thrombosis | 1/131 (0.8%) | 0/129 (0%) | ||
| Stridor | 0/131 (0%) | 1/129 (0.8%) | ||
| Interstitial lung disease | 0/131 (0%) | 1/129 (0.8%) | ||
| Respiratory failure | 2/131 (1.5%) | 2/129 (1.6%) | ||
| Pulmonary embolism | 2/131 (1.5%) | 2/129 (1.6%) | ||
| Vascular disorders | ||||
| Arterial haemorrhage | 0/131 (0%) | 1/129 (0.8%) | ||
| Peripheral ischaemia | 1/131 (0.8%) | 0/129 (0%) | ||
| Superior vena cava syndrome | 0/131 (0%) | 1/129 (0.8%) | ||
Other (Not Including Serious) Adverse Events |
||||
| NIVOLUMAB | DOCETAXEL | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 114/131 (87%) | 119/129 (92.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 22/131 (16.8%) | 37/129 (28.7%) | ||
| Leukopenia | 1/131 (0.8%) | 9/129 (7%) | ||
| Neutropenia | 1/131 (0.8%) | 41/129 (31.8%) | ||
| Gastrointestinal disorders | ||||
| Vomiting | 10/131 (7.6%) | 17/129 (13.2%) | ||
| Diarrhoea | 20/131 (15.3%) | 33/129 (25.6%) | ||
| Nausea | 20/131 (15.3%) | 32/129 (24.8%) | ||
| Abdominal pain | 7/131 (5.3%) | 9/129 (7%) | ||
| Constipation | 17/131 (13%) | 19/129 (14.7%) | ||
| General disorders | ||||
| Pyrexia | 20/131 (15.3%) | 24/129 (18.6%) | ||
| Chest pain | 10/131 (7.6%) | 12/129 (9.3%) | ||
| Chills | 7/131 (5.3%) | 1/129 (0.8%) | ||
| Mucosal inflammation | 3/131 (2.3%) | 13/129 (10.1%) | ||
| Fatigue | 40/131 (30.5%) | 51/129 (39.5%) | ||
| Asthenia | 20/131 (15.3%) | 27/129 (20.9%) | ||
| Oedema peripheral | 10/131 (7.6%) | 16/129 (12.4%) | ||
| Infections and infestations | ||||
| Upper respiratory tract infection | 7/131 (5.3%) | 4/129 (3.1%) | ||
| Bronchitis | 12/131 (9.2%) | 4/129 (3.1%) | ||
| Investigations | ||||
| Neutrophil count decreased | 0/131 (0%) | 8/129 (6.2%) | ||
| Weight decreased | 12/131 (9.2%) | 6/129 (4.7%) | ||
| White blood cell count decreased | 0/131 (0%) | 8/129 (6.2%) | ||
| Metabolism and nutrition disorders | ||||
| Hypercalcaemia | 8/131 (6.1%) | 0/129 (0%) | ||
| Hypomagnesaemia | 7/131 (5.3%) | 4/129 (3.1%) | ||
| Decreased appetite | 32/131 (24.4%) | 35/129 (27.1%) | ||
| Hyperglycaemia | 9/131 (6.9%) | 10/129 (7.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Bone pain | 2/131 (1.5%) | 7/129 (5.4%) | ||
| Musculoskeletal chest pain | 7/131 (5.3%) | 3/129 (2.3%) | ||
| Myalgia | 3/131 (2.3%) | 15/129 (11.6%) | ||
| Back pain | 12/131 (9.2%) | 11/129 (8.5%) | ||
| Arthralgia | 13/131 (9.9%) | 16/129 (12.4%) | ||
| Musculoskeletal pain | 8/131 (6.1%) | 7/129 (5.4%) | ||
| Nervous system disorders | ||||
| Paraesthesia | 4/131 (3.1%) | 8/129 (6.2%) | ||
| Headache | 18/131 (13.7%) | 9/129 (7%) | ||
| Dizziness | 11/131 (8.4%) | 12/129 (9.3%) | ||
| Neuropathy peripheral | 4/131 (3.1%) | 15/129 (11.6%) | ||
| Psychiatric disorders | ||||
| Insomnia | 7/131 (5.3%) | 6/129 (4.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 46/131 (35.1%) | 38/129 (29.5%) | ||
| Haemoptysis | 8/131 (6.1%) | 9/129 (7%) | ||
| Cough | 40/131 (30.5%) | 24/129 (18.6%) | ||
| Dysphonia | 9/131 (6.9%) | 1/129 (0.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 10/131 (7.6%) | 3/129 (2.3%) | ||
| Rash | 10/131 (7.6%) | 11/129 (8.5%) | ||
| Alopecia | 1/131 (0.8%) | 29/129 (22.5%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01642004
Other Study ID Numbers:
- CA209-017
- 2011-004792-36
First Posted:
Jul 17, 2012
Last Update Posted:
Feb 7, 2022
Last Verified:
Jan 1, 2022