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

Non-Squamous Cell Non-small Cell Lung Cancer Clinical Trial

— CheckMate057  

Official title:

An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01673867
• Other study ID #: CA209-057
• Secondary ID: 2012-002472-14
• Status: Completed
• Phase: Phase 3
• Start date: November 2, 2012
• Est. completion date: December 17, 2021

Study information

• Verified date: January 2023
• 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 (Nivolumab) as compared with Docetaxel in subjects with non-squamous cell non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy

Description:

CheckMate 057: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 057

Recruitment information / eligibility

• Status: Completed
• Enrollment: 582
• Est. completion date: December 17, 2021
• Est. primary completion date: February 5, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men & women =18 years of age

• Subjects with histologically or cytologically-documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease) and who will receive study therapy as second or third line of treatment for 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 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 asymptomatic or 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 =10mg daily prednisone (or equivalent)

• Subjects with carcinomatous meningitis

• Subjects with active or recent history of known or suspected autoimmune disease. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment 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 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)

• Prior treatment with Docetaxel

• Treatment with any investigational agent within 14 days of first administration of study treatment

Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

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

Intervention

Biological:
• Nivolumab

Drug:
• Docetaxel

Locations

Country	Name	City	State
Argentina	Local Institution - 0011	Buenos Aires
Argentina	Local Institution - 0010	Capital Federal	Buenos Aires
Argentina	Local Institution - 0057	Capital Federal	Buenos Aires
Argentina	Local Institution - 0124	Ciudad De Buenos Aires	Buenos Aires
Argentina	Local Institution - 0125	La Rioja
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Frankston	Victoria
Australia	Local Institution	Kurralta Park	South Australia
Australia	Local Institution	Melbourne	Victoria
Australia	Local Institution	Tweed Heads	New South Wales
Australia	Local Institution	Woolloongabba	Queensland
Austria	Local Institution	Linz
Austria	Local Institution	Salzburg
Austria	Local Institution	Vienna
Austria	Local Institution	Wels
Brazil	Local Institution - 0052	Barretos	Sao Paulo
Brazil	Local Institution - 0056	Fortaleza	Ceara
Brazil	Local Institution - 0053	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution - 0055	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution - 0051	Rio De Janeiro
Brazil	Local Institution - 0054	Salvador	Bahia
Canada	Local Institution - 0133	Edmonton	Alberta
Canada	Local Institution	London	Ontario
Canada	Local Institution - 0110	Rimouski	Quebec
Chile	Local Institution - 0058	Santiago	Metropolitana
Chile	Local Institution - 0077	Santiago	Metropolitana
Chile	Local Institution - 0134	Santiago	Metropolitana
Chile	Local Institution - 0012	Viña Del Mar	Valparaiso
Czechia	Local Institution - 0018	Praha 8
France	Local Institution	Creteil
France	Local Institution	Dijon Cedex
France	Local Institution - 0119	La Roche Sur Yon Cedex 9
France	Local Institution - 0113	Lyon Cedex 08
France	Local Institution - 0112	Marseille Cedex 20
France	Local Institution	Poitiers
France	Local Institution - 0114	Rennes Cedex 9
France	Local Institution	Toulouse
Germany	Local Institution	Bad Berka
Germany	Local Institution	Grosshansdorf
Germany	Local Institution	Heidelberg
Germany	Local Institution - 0090	Koeln
Germany	Local Institution	Mainz
Germany	Local Institution	Recklinghausen
Germany	Local Institution	Stuttgart
Germany	Local Institution	Ulm
Hong Kong	Local Institution	Hong Kong
Hong Kong	Local Institution - 0043	Hong Kong
Hungary	Local Institution - 0074	Budapest
Italy	Local Institution - 0122	Bergamo
Italy	Local Institution - 0086	Bologna
Italy	Local Institution - 0087	Meldola (fc)
Italy	Local Institution - 0085	Milano
Italy	Local Institution - 0084	Padova
Italy	Local Institution - 0121	Parma
Italy	Local Institution - 0083	Perugia
Italy	Local Institution - 0088	Ravenna
Italy	Local Institution - 0082	Siena
Mexico	Local Institution	Hermosillo	Sonora
Mexico	Local Institution - 0107	Mexico	Distrito Federal
Mexico	Local Institution - 0108	Mexico	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Norway	Local Institution - 0141	Oslo
Peru	Local Institution - 0050	Arequipa
Peru	Local Institution - 0048	Lima
Peru	Local Institution - 0049	Lima
Peru	Local Institution - 0131	Miraflores	Lima
Poland	Local Institution - 0068	Gdansk
Poland	Local Institution - 0073	Krakow	Malopolskie
Poland	Local Institution - 0072	Olsztyn
Poland	Local Institution - 0067	Szczecin
Poland	Local Institution - 0070	Warszawa
Romania	Local Institution - 0099	Bucuresti
Romania	Local Institution - 0123	Cluj-Napoca
Romania	Local Institution - 0063	Craiova
Romania	Local Institution - 0061	Iasi
Romania	Local Institution - 0062	Timisoara
Russian Federation	Local Institution - 0078	Moscow
Russian Federation	Local Institution - 0079	Moscow
Russian Federation	Local Institution - 0120	Moscow
Russian Federation	Local Institution - 0080	St. Petersburg
Singapore	Local Institution	Singapore
Singapore	Local Institution	Singapore
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution - 0001	Sevilla
Spain	Local Institution	Vizcaya
Switzerland	Local Institution	Basel
Switzerland	Local Institution	Chur
United States	The Johns Hopkins University	Baltimore	Maryland
United States	Local Institution - 0031	Boston	Massachusetts
United States	Local Institution - 0040	Boston	Massachusetts
United States	Local Institution - 0138	Boston	Massachusetts
United States	Local Institution - 0024	Chattanooga	Tennessee
United States	Local Institution - 0030	Chicago	Illinois
United States	Local Institution - 0026	Cincinnati	Ohio
United States	Local Institution - 0025	Columbia	South Carolina
United States	Local Institution - 0033	Dallas	Texas
United States	Local Institution - 0009	Duarte	California
United States	Local Institution - 0027	Durham	North Carolina
United States	Local Institution - 0032	Houston	Texas
United States	Local Institution - 0041	Kennewick	Washington
United States	St. Mary Medical Center	Langhorne	Pennsylvania
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Northwest Georgia Oncology Center, P.C.	Marietta	Georgia
United States	Local Institution - 0008	Mineola	New York
United States	Local Institution - 0019	Morgantown	West Virginia
United States	Local Institution - 0028	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Local Institution - 0020	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Local Institution - 0042	San Diego	California
United States	San Francisco Oncology Associates	San Francisco	California
United States	Local Institution - 0035	Sayre	Pennsylvania
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Local Institution - 0007	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Local Institution - 0034	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Mexico,  Norway,  Peru,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint	Overall survival was defined as the time from randomization to the date of death. A participant who has not died will be censored at last known date alive. OS will be followed continuously while participants are on the study drug and every 3 months via in-person or phone contact after participants discontinue the study drug. Median and hazard ratio computed using Kaplan-Meier method.	Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Secondary	Objective Response Rate (ORR)	ORR was defined as the percentage of participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). BOR was defined as the best investigator-assessed response designation, recorded between the date of randomization and the date of objectively documented progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or the date of subsequent anti-cancer therapy (excluding on-treatment palliative radiotherapy of non-target bone lesions or Central Nervous System (CNS) lesions), whichever occurred first. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CR+PR, confidence interval based on the Clopper and Pearson method.	From randomization to date of objectively documented progression (up to approximately 110 months)
Secondary	Time To Objective Response (TTOR)	Time to Objective Response 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 randomization to the date of first confirmed response (up to approximately 110 months)
Secondary	Duration of Objective Response (DOOR)	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. Median computed using Kaplan-Meier method.	From randomization to date of first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 110 months)
Secondary	Progression-Free Survival (PFS)	PFS was defined as the time from randomization to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Progression will be assessed every 6 weeks (from the first on-study radiographic assessment) until disease progression is noted. Progressive disease was defined as least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Median computed using the Kaplan-Meier method.	From randomization to first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 110 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.	Randomization to Week 12
Secondary	Overall Survival (OS) by PD-L1 Expression at Baseline	Overall survival was defined as the time from randomization to the date of death. A participant who has not died will be censored at last known date alive. Overall Survival time was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. Median computed using the Kaplan-Meier method.	From randomization to the date of death or last known date alive (up to approximately 110 months)
Secondary	Objective Response Rate (ORR) by PD-L1 Expression at Baseline	ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CR+PR, confidence interval based on the Clopper and Pearson method. ORR was reported for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay.	From randomization to date of objectively documented progression (up to approximately 110 months)

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