Clinical trial NCT01673867: Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Squamous Cell Non-small Cell Lung Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-08-28
Enrollment: 582
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed description: CheckMate 057: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 057

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint
timeFrame: Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From randomization to date of objectively documented progression (up to approximately 110 months)
measure: Time To Objective Response (TTOR)
timeFrame: From randomization to the date of first confirmed response (up to approximately 110 months)
measure: Duration of Objective Response (DOOR)
timeFrame: From randomization to date of first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 110 months)
measure: Progression-Free Survival (PFS)
timeFrame: 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)
measure: Percentage of Participants Experiencing Disease-Related Symptom Improvement by Week 12
timeFrame: Randomization to Week 12
measure: Overall Survival (OS) by PD-L1 Expression at Baseline
timeFrame: From randomization to the date of death or last known date alive (up to approximately 110 months)
measure: Objective Response Rate (ORR) by PD-L1 Expression at Baseline
timeFrame: From randomization to date of objectively documented progression (up to approximately 110 months)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: Local Institution - 0009
state: California
city: San Diego
country: United States
facility: Local Institution - 0042
state: California
city: San Francisco
country: United States
facility: San Francisco Oncology Associates
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Tampa
country: United States
facility: Local Institution - 0034
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Center, P.C.
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0030
state: Illinois
city: Baltimore
country: United States
facility: The Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0031
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0040
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0138
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Mineola
country: United States
facility: Local Institution - 0008
state: New York
city: New York
country: United States
facility: Local Institution - 0020
state: New York
city: Durham
country: United States
facility: Local Institution - 0027
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution - 0026
state: Ohio
city: Langhorne
country: United States
facility: St. Mary Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Sayre
country: United States
facility: Local Institution - 0035
state: Pennsylvania
city: Columbia
country: United States
facility: Local Institution - 0025
state: South Carolina
city: Chattanooga
country: United States
facility: Local Institution - 0024
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0028
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 0033
state: Texas
city: Houston
country: United States
facility: Local Institution - 0032
state: Texas
city: Kennewick
country: United States
facility: Local Institution - 0041
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Local Institution - 0007
state: Washington
city: Morgantown
country: United States
facility: Local Institution - 0019
state: West Virginia
city: Capital Federal
country: Argentina
facility: Local Institution - 0010
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution - 0057
state: Buenos Aires
city: Ciudad De Buenos Aires
country: Argentina
facility: Local Institution - 0124
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0011
city: La Rioja
country: Argentina
facility: Local Institution - 0125
city: Tweed Heads
country: Australia
facility: Local Institution
state: New South Wales
city: Woolloongabba
country: Australia
facility: Local Institution
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Kurralta Park
country: Australia
facility: Local Institution
state: South Australia
city: Frankston
country: Australia
facility: Local Institution
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Linz
country: Austria
facility: Local Institution
city: Salzburg
country: Austria
facility: Local Institution
city: Vienna
country: Austria
facility: Local Institution
city: Wels
country: Austria
facility: Local Institution
city: Salvador
country: Brazil
facility: Local Institution - 0054
state: Bahia
city: Fortaleza
country: Brazil
facility: Local Institution - 0056
state: Ceara
city: Porto Alegre
country: Brazil
facility: Local Institution - 0053
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution - 0055
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Local Institution - 0052
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution - 0051
city: Edmonton
country: Canada
facility: Local Institution - 0133
state: Alberta
city: London
country: Canada
facility: Local Institution
state: Ontario
city: Rimouski
country: Canada
facility: Local Institution - 0110
state: Quebec
city: Santiago
country: Chile
facility: Local Institution - 0058
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0077
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0134
state: Metropolitana
city: Viña Del Mar
country: Chile
facility: Local Institution - 0012
state: Valparaiso
city: Praha 8
country: Czechia
facility: Local Institution - 0018
city: Creteil
country: France
facility: Local Institution
city: Dijon Cedex
country: France
facility: Local Institution
city: La Roche Sur Yon Cedex 9
country: France
facility: Local Institution - 0119
city: Lyon Cedex 08
country: France
facility: Local Institution - 0113
city: Marseille Cedex 20
country: France
facility: Local Institution - 0112
city: Poitiers
country: France
facility: Local Institution
city: Rennes Cedex 9
country: France
facility: Local Institution - 0114
city: Toulouse
country: France
facility: Local Institution
city: Bad Berka
country: Germany
facility: Local Institution
city: Grosshansdorf
country: Germany
facility: Local Institution
city: Heidelberg
country: Germany
facility: Local Institution
city: Koeln
country: Germany
facility: Local Institution - 0090
city: Mainz
country: Germany
facility: Local Institution
city: Recklinghausen
country: Germany
facility: Local Institution
city: Stuttgart
country: Germany
facility: Local Institution
city: Ulm
country: Germany
facility: Local Institution
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0043
city: Hong Kong
country: Hong Kong
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution - 0074
city: Bergamo
country: Italy
facility: Local Institution - 0122
city: Bologna
country: Italy
facility: Local Institution - 0086
city: Meldola (fc)
country: Italy
facility: Local Institution - 0087
city: Milano
country: Italy
facility: Local Institution - 0085
city: Padova
country: Italy
facility: Local Institution - 0084
city: Parma
country: Italy
facility: Local Institution - 0121
city: Perugia
country: Italy
facility: Local Institution - 0083
city: Ravenna
country: Italy
facility: Local Institution - 0088
city: Siena
country: Italy
facility: Local Institution - 0082
city: Mexico
country: Mexico
facility: Local Institution - 0107
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution - 0108
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Hermosillo
country: Mexico
facility: Local Institution
state: Sonora
city: Oslo
country: Norway
facility: Local Institution - 0141
city: Miraflores
country: Peru
facility: Local Institution - 0131
state: Lima
city: Arequipa
country: Peru
facility: Local Institution - 0050
city: Lima
country: Peru
facility: Local Institution - 0048
city: Lima
country: Peru
facility: Local Institution - 0049
city: Krakow
country: Poland
facility: Local Institution - 0073
state: Małopolskie
city: Gdansk
country: Poland
facility: Local Institution - 0068
city: Olsztyn
country: Poland
facility: Local Institution - 0072
city: Szczecin
country: Poland
facility: Local Institution - 0067
city: Warszawa
country: Poland
facility: Local Institution - 0070
city: Bucuresti
country: Romania
facility: Local Institution - 0099
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0123
city: Craiova
country: Romania
facility: Local Institution - 0063
city: Iasi
country: Romania
facility: Local Institution - 0061
city: Timisoara
country: Romania
facility: Local Institution - 0062
city: Moscow
country: Russian Federation
facility: Local Institution - 0078
city: Moscow
country: Russian Federation
facility: Local Institution - 0079
city: Moscow
country: Russian Federation
facility: Local Institution - 0120
city: St. Petersburg
country: Russian Federation
facility: Local Institution - 0080
city: Singapore
country: Singapore
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution - 0001
city: Vizcaya
country: Spain
facility: Local Institution
city: Basel
country: Switzerland
facility: Local Institution
city: Chur
country: Switzerland
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Borghaei H, Gettinger S, Vokes EE, Chow LQM, Burgio MA, de Castro Carpeno J, Pluzanski A, Arrieta O, Frontera OA, Chiari R, Butts C, Wojcik-Tomaszewska J, Coudert B, Garassino MC, Ready N, Felip E, Garcia MA, Waterhouse D, Domine M, Barlesi F, Antonia S, Wohlleber M, Gerber DE, Czyzewicz G, Spigel DR, Crino L, Eberhardt WEE, Li A, Marimuthu S, Brahmer J. Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Mar 1;39(7):723-733. doi: 10.1200/JCO.20.01605. Epub 2021 Jan 15.
citation: Long GV, Tykodi SS, Schneider JG, Garbe C, Gravis G, Rashford M, Agrawal S, Grigoryeva E, Bello A, Roy A, Rollin L, Zhao X. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018 Nov 1;29(11):2208-2213. doi: 10.1093/annonc/mdy408.
citation: Reck M, Brahmer J, Bennett B, Taylor F, Penrod JR, DeRosa M, Dastani H, Spigel DR, Gralla RJ. Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Eur J Cancer. 2018 Oct;102:23-30. doi: 10.1016/j.ejca.2018.05.005. Epub 2018 Aug 10.
citation: Vokes EE, Ready N, Felip E, Horn L, Burgio MA, Antonia SJ, Aren Frontera O, Gettinger S, Holgado E, Spigel D, Waterhouse D, Domine M, Garassino M, Chow LQM, Blumenschein G Jr, Barlesi F, Coudert B, Gainor J, Arrieta O, Brahmer J, Butts C, Steins M, Geese WJ, Li A, Healey D, Crino L. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol. 2018 Apr 1;29(4):959-965. doi: 10.1093/annonc/mdy041.
citation: Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, Poddubskaya E, Borghaei H, Felip E, Paz-Ares L, Pluzanski A, Reckamp KL, Burgio MA, Kohlhaeufl M, Waterhouse D, Barlesi F, Antonia S, Arrieta O, Fayette J, Crino L, Rizvi N, Reck M, Hellmann MD, Geese WJ, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Eberhardt WEE. Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017 Dec 10;35(35):3924-3933. doi: 10.1200/JCO.2017.74.3062. Epub 2017 Oct 12.
citation: Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.