Clinical trial NCT01642004: Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Squamous Cell Non-small Cell Lung Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-07-17
Enrollment: 272
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 as compared with Docetaxel in subjects with squamous cell non-small cell lung cancer (NSCLC), after failure of prior platinum-based chemotherapy.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint
timeFrame: Randomization until 199 deaths, up to November 2014, approximately 25 months
measure: Overall Survival (OS) Rate in All Randomized Participants
timeFrame: Randomization to 18 months post-randomization, up to June 2015
measure: Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint
timeFrame: Randomization until 199 deaths, up to November 2014, approximately 25 months
Secondary outcomes:
measure: Objective Response Rate (ORR) in All Randomized Participants
timeFrame: From the date of randomization up to the date of objectively documented progression, up to approximately 103 months
measure: Time To Response (TTR) in Months for All Confirmed Responders
timeFrame: From the date of randomization to the date of the first confirmed response, up to approximately 12 months
measure: Duration of Objective Response (DOR) in Months for All Confirmed Responders
timeFrame: 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
measure: Progression Free Survival Rate (PFSR)
timeFrame: From randomization to specified timepoints, up to 84 months
measure: Progression-Free Survival (PFS) Time in Months for All Randomized Participants
timeFrame: 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
measure: Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12
timeFrame: From randomization up to Week 12
measure: Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants
timeFrame: From the date of randomization to the date of death from any cause, up to approximately 103 months
measure: Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants
timeFrame: From the date of randomization up to the date of objectively documented progression, up to approximately 103 months
measure: Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants
timeFrame: 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
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona - Scottsdale
state: Arizona
city: Duarte
country: United States
facility: City Of Hope
state: California
city: Duarte
country: United States
facility: Local Institution - 0020
state: California
city: New Haven
country: United States
facility: Local Institution - 0009
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Tampa
country: United States
facility: Local Institution - 0004
state: Florida
city: Marietta
country: United States
facility: Local Institution - 0153
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0100
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Local Institution - 0003
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0036
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0084
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0150
state: Massachusetts
city: Mineola
country: United States
facility: Local Institution - 0016
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Local Institution - 0006
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Durham
country: United States
facility: Local Institution - 0008
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
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: Philadelphia
country: United States
facility: Local Institution - 0011
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Medical Group, Pc
state: Pennsylvania
city: Columbia
country: United States
facility: Local Institution - 0082
state: South Carolina
city: Chattanooga
country: United States
facility: Local Institution - 0087
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0005
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0032
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 0012
state: Texas
city: Dallas
country: United States
facility: University Of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Local Institution - 0086
state: Texas
city: Seattle
country: United States
facility: Local Institution - 0017
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Local Institution - 0001
state: Washington
city: Seattle
country: United States
facility: University of Washington - Seattle Cancer Care Alliance
state: Washington
city: Morgantown
country: United States
facility: Local Institution - 0033
state: West Virginia
city: Capital Federal
country: Argentina
facility: Local Institution - 0116
state: Buenos Aires
city: Ciudad Autónoma De Buenos Aire
country: Argentina
facility: Local Institution - 0072
state: Buenos Aires
city: San Miguel De Tucuman
country: Argentina
facility: Local Institution - 0164
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Local Institution - 0071
city: Cordoba
country: Argentina
facility: Local Institution - 0141
city: Wollongong
country: Australia
facility: Local Institution - 0073
state: New South Wales
city: Adelaide
country: Australia
facility: Local Institution - 0159
state: South Australia
city: Elizabeth Vale
country: Australia
facility: Local Institution - 0140
state: South Australia
city: Kurralta Park
country: Australia
facility: Local Institution - 0158
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 0085
state: Victoria
city: Linz
country: Austria
facility: Local Institution - 0102
city: Salzburg
country: Austria
facility: Local Institution - 0104
city: Vienna
country: Austria
facility: Local Institution - 0049
city: Wels
country: Austria
facility: Local Institution - 0103
city: Winnipeg
country: Canada
facility: Local Institution - 0146
state: Manitoba
city: Montreal
country: Canada
facility: Local Institution - 0147
state: Quebec
city: Rimouski
country: Canada
facility: Local Institution - 0152
state: Quebec
city: Santiago
country: Chile
facility: Local Institution - 0117
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0131
state: Metropolitana
city: Viña Del Mar
country: Chile
facility: Local Institution - 0110
state: Valparaiso
city: Antofagasta
country: Chile
facility: Local Institution - 0161
city: Santiago
country: Chile
facility: Local Institution - 0154
city: Praha 8
country: Czechia
facility: Local Institution - 0111
city: Avignon Cedes 9
country: France
facility: Local Institution - 0053
city: Caen
country: France
facility: Local Institution - 0156
city: Dijon
country: France
facility: Local Institution - 0025
city: Dijon
country: France
facility: Local Institution
city: La Roche Sur Yon Cedex 9
country: France
facility: Local Institution - 0093
city: Lyon Cedex 08
country: France
facility: Local Institution - 0022
city: Lyon Cedex 08
country: France
facility: Local Institution
city: Marseille Cedex 20
country: France
facility: Local Institution - 0023
city: Marseille Cedex 20
country: France
facility: Local Institution
city: Pierre Benite
country: France
facility: Local Institution - 0160
city: Rennes Cedex 9
country: France
facility: Local Institution - 0027
city: Rennes Cedex 9
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution - 0157
city: Toulouse
country: France
facility: Local Institution - 0040
city: Bad Berka
country: Germany
facility: Local Institution - 0064
city: Essen
country: Germany
facility: Local Institution - 0105
city: Gerlingen
country: Germany
facility: Local Institution - 0109
city: Grosshansdorf
country: Germany
facility: Local Institution - 0048
city: Heidelberg
country: Germany
facility: Local Institution - 0065
city: Koeln
country: Germany
facility: Local Institution - 0063
city: Krefeld
country: Germany
facility: Local Institution - 0162
city: Budapest
country: Hungary
facility: Local Institution - 0095
city: Budapest
country: Hungary
facility: Local Institution - 0096
city: Dublin 8
country: Ireland
facility: Local Institution - 0039
state: Dublin
city: Dublin 9
country: Ireland
facility: Local Institution - 0035
state: Dublin
city: Bologna
country: Italy
facility: Local Institution - 0058
city: Meldola (fc)
country: Italy
facility: Local Institution - 0088
city: Milano
country: Italy
facility: Local Institution - 0057
city: Padova
country: Italy
facility: Local Institution - 0056
city: Perugia
country: Italy
facility: Local Institution - 0055
city: Ravenna
country: Italy
facility: Local Institution - 0089
city: Siena
country: Italy
facility: Local Institution - 0054
city: Mexico
country: Mexico
facility: Local Institution - 0107
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution - 0108
state: Distrito Federal
city: Leon, Guanajato
country: Mexico
facility: Local Institution - 0106
state: Guanajuato
city: Hermosillo
country: Mexico
facility: Local Institution - 0139
state: Sonora
city: Amsterdam
country: Netherlands
facility: Local Institution - 0052
city: Rotterdam
country: Netherlands
facility: Local Institution - 0051
city: Oslo
country: Norway
facility: Local Institution - 0143
city: Arequipa
country: Peru
facility: Local Institution - 0099
city: Lima
country: Peru
facility: Local Institution - 0061
city: Gdansk
country: Poland
facility: Local Institution - 0126
city: Krakow
country: Poland
facility: Local Institution - 0130
city: Olsztyn
country: Poland
facility: Local Institution - 0129
city: Szczecin
country: Poland
facility: Local Institution - 0124
city: Warszawa
country: Poland
facility: Local Institution - 0127
city: Bucuresti
country: Romania
facility: Local Institution - 0136
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0145
city: Constanta
country: Romania
facility: Local Institution - 0138
city: Craiova
country: Romania
facility: Local Institution - 0121
city: Iasi
country: Romania
facility: Local Institution - 0119
city: Timisoara
country: Romania
facility: Local Institution - 0120
city: Moscow
country: Russian Federation
facility: Local Institution - 0132
city: Moscow
country: Russian Federation
facility: Local Institution - 0133
city: Moscow
country: Russian Federation
facility: Local Institution - 0144
city: St. Petersburg
country: Russian Federation
facility: Local Institution - 0135
city: Barakaldo
country: Spain
facility: Local Institution - 0044
state: Vizcaya
city: Barcelona
country: Spain
facility: Local Institution - 0042
city: Madrid
country: Spain
facility: Local Institution - 0046
city: Madrid
country: Spain
facility: Local Institution - 0045
city: Sevilla
country: Spain
facility: Local Institution - 0041
city: Cottingham
country: United Kingdom
facility: Local Institution - 0047
state: East Yorkshire
city: Southampton
country: United Kingdom
facility: Local Institution - 0034
state: Hampshire
city: Withington
country: United Kingdom
facility: Local Institution - 0163
state: Manchester
city: Sheffield
country: United Kingdom
facility: Local Institution - 0037
state: Yorkshire
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: Dercle L, Fronheiser M, Lu L, Du S, Hayes W, Leung DK, Roy A, Wilkerson J, Guo P, Fojo AT, Schwartz LH, Zhao B. Identification of Non-Small Cell Lung Cancer Sensitive to Systemic Cancer Therapies Using Radiomics. Clin Cancer Res. 2020 May 1;26(9):2151-2162. doi: 10.1158/1078-0432.CCR-19-2942. Epub 2020 Mar 20.
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: 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: Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.