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

Squamous Cell Non-small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01642004
• Other study ID #: CA209-017
• Secondary ID: 2011-004792-36
• Status: Completed
• Phase: Phase 3
• Start date: October 16, 2012
• Est. completion date: August 16, 2021

Study information

• Verified date: November 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: August 16, 2021
• Est. primary completion date: November 17, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Squamous Cell Non-small Cell Lung Cancer

Intervention

Biological:
• Nivolumab

Drug:
• Docetaxel

Locations

Country	Name	City	State
Argentina	Local Institution - 0071	Buenos Aires
Argentina	Local Institution - 0116	Capital Federal	Buenos Aires
Argentina	Local Institution - 0072	Ciudad Autónoma De Buenos Aire	Buenos Aires
Argentina	Local Institution - 0141	Cordoba
Argentina	Local Institution - 0164	San Miguel De Tucuman	Tucuman
Australia	Local Institution - 0159	Adelaide	South Australia
Australia	Local Institution - 0085	Clayton	Victoria
Australia	Local Institution - 0140	Elizabeth Vale	South Australia
Australia	Local Institution - 0158	Kurralta Park	South Australia
Australia	Local Institution - 0073	Wollongong	New South Wales
Austria	Local Institution - 0102	Linz
Austria	Local Institution - 0104	Salzburg
Austria	Local Institution - 0049	Vienna
Austria	Local Institution - 0103	Wels
Canada	Local Institution - 0147	Montreal	Quebec
Canada	Local Institution - 0152	Rimouski	Quebec
Canada	Local Institution - 0146	Winnipeg	Manitoba
Chile	Local Institution - 0161	Antofagasta
Chile	Local Institution - 0117	Santiago	Metropolitana
Chile	Local Institution - 0131	Santiago	Metropolitana
Chile	Local Institution - 0154	Santiago
Chile	Local Institution - 0110	Viña Del Mar	Valparaiso
Czechia	Local Institution - 0111	Praha 8
France	Local Institution - 0053	Avignon Cedes 9
France	Local Institution - 0156	Caen
France	Local Institution	Dijon
France	Local Institution - 0025	Dijon
France	Local Institution - 0093	La Roche Sur Yon Cedex 9
France	Local Institution	Lyon Cedex 08
France	Local Institution - 0022	Lyon Cedex 08
France	Local Institution	Marseille Cedex 20
France	Local Institution - 0023	Marseille Cedex 20
France	Local Institution - 0160	Pierre Benite
France	Local Institution	Rennes Cedex 9
France	Local Institution - 0027	Rennes Cedex 9
France	Local Institution - 0157	Strasbourg
France	Local Institution - 0040	Toulouse
Germany	Local Institution - 0064	Bad Berka
Germany	Local Institution - 0105	Essen
Germany	Local Institution - 0109	Gerlingen
Germany	Local Institution - 0048	Grosshansdorf
Germany	Local Institution - 0065	Heidelberg
Germany	Local Institution - 0063	Koeln
Germany	Local Institution - 0162	Krefeld
Hungary	Local Institution - 0095	Budapest
Hungary	Local Institution - 0096	Budapest
Ireland	Local Institution - 0039	Dublin 8	Dublin
Ireland	Local Institution - 0035	Dublin 9	Dublin
Italy	Local Institution - 0058	Bologna
Italy	Local Institution - 0088	Meldola (fc)
Italy	Local Institution - 0057	Milano
Italy	Local Institution - 0056	Padova
Italy	Local Institution - 0055	Perugia
Italy	Local Institution - 0089	Ravenna
Italy	Local Institution - 0054	Siena
Mexico	Local Institution - 0139	Hermosillo	Sonora
Mexico	Local Institution - 0106	Leon, Guanajato	Guanajuato
Mexico	Local Institution - 0107	Mexico	Distrito Federal
Mexico	Local Institution - 0108	Mexico	Distrito Federal
Netherlands	Local Institution - 0052	Amsterdam
Netherlands	Local Institution - 0051	Rotterdam
Norway	Local Institution - 0143	Oslo
Peru	Local Institution - 0099	Arequipa
Peru	Local Institution - 0061	Lima
Poland	Local Institution - 0126	Gdansk
Poland	Local Institution - 0130	Krakow
Poland	Local Institution - 0129	Olsztyn
Poland	Local Institution - 0124	Szczecin
Poland	Local Institution - 0127	Warszawa
Romania	Local Institution - 0136	Bucuresti
Romania	Local Institution - 0145	Cluj-Napoca
Romania	Local Institution - 0138	Constanta
Romania	Local Institution - 0121	Craiova
Romania	Local Institution - 0119	Iasi
Romania	Local Institution - 0120	Timisoara
Russian Federation	Local Institution - 0132	Moscow
Russian Federation	Local Institution - 0133	Moscow
Russian Federation	Local Institution - 0144	Moscow
Russian Federation	Local Institution - 0135	St. Petersburg
Spain	Local Institution - 0044	Barakaldo	Vizcaya
Spain	Local Institution - 0042	Barcelona
Spain	Local Institution - 0045	Madrid
Spain	Local Institution - 0046	Madrid
Spain	Local Institution - 0041	Sevilla
United Kingdom	Local Institution - 0047	Cottingham	East Yorkshire
United Kingdom	Local Institution - 0037	Sheffield	Yorkshire
United Kingdom	Local Institution - 0034	Southampton	Hampshire
United Kingdom	Local Institution - 0163	Withington	Manchester
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Local Institution - 0003	Baltimore	Maryland
United States	Local Institution - 0036	Boston	Massachusetts
United States	Local Institution - 0084	Boston	Massachusetts
United States	Local Institution - 0150	Boston	Massachusetts
United States	Local Institution - 0087	Chattanooga	Tennessee
United States	Local Institution - 0100	Chicago	Illinois
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Local Institution - 0082	Columbia	South Carolina
United States	Local Institution - 0012	Dallas	Texas
United States	University Of Texas Southwestern Medical Center	Dallas	Texas
United States	City Of Hope	Duarte	California
United States	Local Institution - 0020	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Local Institution - 0008	Durham	North Carolina
United States	Local Institution - 0086	Houston	Texas
United States	St Mary Medical Center	Langhorne	Pennsylvania
United States	Local Institution - 0153	Marietta	Georgia
United States	Local Institution - 0016	Mineola	New York
United States	Winthrop University Hospital	Mineola	New York
United States	Local Institution - 0033	Morgantown	West Virginia
United States	Local Institution - 0005	Nashville	Tennessee
United States	Local Institution - 0032	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Local Institution - 0009	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Local Institution - 0006	New York	New York
United States	Memorial Sloan Kettering Nassau	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Local Institution - 0011	Philadelphia	Pennsylvania
United States	Guthrie Medical Group, Pc	Sayre	Pennsylvania
United States	Mayo Clinic in Arizona - Scottsdale	Scottsdale	Arizona
United States	Local Institution - 0001	Seattle	Washington
United States	Local Institution - 0017	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	Local Institution - 0004	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Canada,  Chile,  Czechia,  France,  Germany,  Hungary,  Ireland,  Italy,  Mexico,  Netherlands,  Norway,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint	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.	Randomization until 199 deaths, up to November 2014, approximately 25 months
Primary	Overall Survival (OS) Rate in All Randomized Participants	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.	Randomization to 18 months post-randomization, up to June 2015
Primary	Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint	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.	Randomization until 199 deaths, up to November 2014, approximately 25 months
Secondary	Objective Response Rate (ORR) in All Randomized Participants	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.	From the date of randomization up to the date of objectively documented progression, up to approximately 103 months
Secondary	Time To Response (TTR) in Months for All Confirmed Responders	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.	From the date of randomization to the date of the first confirmed response, up to approximately 12 months
Secondary	Duration of Objective Response (DOR) in Months for All Confirmed Responders	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.	From the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 94 months
Secondary	Progression Free Survival Rate (PFSR)	PFSR was defined as the percentage of participants who did not experience disease progression or death from any cause at a given time point following randomization. Progression was assessed by investigators according to RECIST v1.1. 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.	From randomization to specified timepoints, up to 84 months
Secondary	Progression-Free Survival (PFS) Time in Months for All Randomized Participants	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.	From randomization up to the first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 103 months
Secondary	Percentage of Participants Experiencing Disease-related Symptom Improvement by 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.	From randomization up to Week 12
Secondary	Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants	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.	From the date of randomization to the date of death from any cause, up to approximately 103 months
Secondary	Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants	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.	From the date of randomization up to the date of objectively documented progression, up to approximately 103 months
Secondary	Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants	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.	From the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 103 months

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