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Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC (CheckMate057)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01673867
First received: August 24, 2012
Last updated: July 18, 2016
Last verified: January 2016
  Purpose
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

Condition Intervention Phase
Non-Squamous Cell Non-small Cell Lung Cancer
Biological: Nivolumab
Drug: Docetaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]
    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 380 deaths, with the actual analysis occurring at 413 deaths.

  • One-year Overall Survival (OS) Rate in All Randomized Participants [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The one-year overall survival rate is a percentage, representing the fraction of all randomized participants who were alive following one year of treatment. 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 [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]
    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 380 deaths, with the actual analysis occurring at 413 deaths.


Secondary Outcome Measures:
  • Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]

    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. CIs were computed using the Clopper and Pearson method.


  • Duration of Objective Response (DOR) in Months for All Confirmed Responders at Primary Endpoint [ Time Frame: Date of confirmed response to date of documented tumor progression or death, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]

    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 To Response (TTR) in Months for All Confirmed Responders at Primary Endpoint [ Time Frame: Randomization until confirmed response, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]
    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.

  • Progression-Free Survival (PFS) Rate at 12 Months [ Time Frame: Randomization to 12 months ] [ Designated as safety issue: No ]
    PFS rate was defined as the percentage of participants experiencing no disease progression or death from any cause at 12 months after randomization. Progression was assessed by investigators according to RECIST v1.1. 95% CIs were estimated using the Kaplan-Meier method.

  • Progression-Free Survival (PFS) Time in Months for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]
    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% CIs for median PFS were computed by Brookmeyer and Crowley method (using log-log transformation). Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.

  • Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12 [ Time Frame: Randomization to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]
    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. Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.

  • Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]
    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. 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. CIs were computed using the Clopper and Pearson method.


Enrollment: 792
Study Start Date: October 2012
Estimated Study Completion Date: January 2017
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Nivolumab
Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Biological: Nivolumab
Other Name: BMS-936558 (Anti-PD1)
Active Comparator: 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
Drug: Docetaxel
Other Name: Taxotere®

Detailed Description:
CheckMate 057: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 057
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673867

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, California
City Of Hope National Medical Center
Duarte, California, United States, 91010
Sharp Clinical Oncology Research
San Diego, California, United States, 92123
San Francisco Oncology Associates
San Francisco, California, United States, 94115
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Northwest Georgia Oncology Center, P.C.
Marietta, Georgia, United States, 30060
United States, Illinois
University Of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Winthrop University Hospital
Mineola, New York, United States, 11501
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Pennsylvania
St. Mary Medical Center
Langhorne, Pennsylvania, United States, 19047
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Guthrie Clinic, Ltd
Sayre, Pennsylvania, United States, 18840
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
United States, Tennessee
Tennessee Oncology, Pllc
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, Pllc
Nashville, Tennessee, United States, 37203
Henry-Joyce Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
University Of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Univ Of Tx. Md Anderson
Houston, Texas, United States, 77030
United States, Washington
Columbia Basin Hematology And Oncology
Kennewick, Washington, United States, 99336
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
United States, West Virginia
West Virginia University-Mbrcc
Morgantown, West Virginia, United States, 26506
Argentina
Local Institution
Capital Federal, Buenos Aires, Argentina, 1426
Local Institution
Capital Federal, Buenos Aires, Argentina, 1431
Local Institution
Ciudad De Buenos Aires, Buenos Aires, Argentina, C1181ACH
Local Institution
Buenos Aires, Argentina, 1417
Local Institution
Buenos Aires, Argentina, C1280AEB
Local Institution
La Rioja, Argentina, 5300
Australia, New South Wales
Local Institution
Tweed Heads, New South Wales, Australia, 2485
Australia, Queensland
Local Institution
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Local Institution
Adelaide, South Australia, Australia, 5000
Local Institution
Kurralta Park, South Australia, Australia, 5037
Australia, Victoria
Local Institution
Frankston, Victoria, Australia, 3199
Local Institution
Melbourne, Victoria, Australia, 3065
Austria
Local Institution
Linz, Austria, 4020
Local Institution
Salzburg, Austria, 5020
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Vienna, Austria, 1130
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Wels, Austria, 4600
Brazil
Local Institution
Salvador, Bahia, Brazil, 40170
Local Institution
Fortaleza, Ceara, Brazil, 60336
Local Institution
Porto Alegre, Rio Grande Do Sul, Brazil, 90020
Local Institution
Porto Alegre, Rio Grande Do Sul, Brazil, 90610
Local Institution
Barretos, Sao Paulo, Brazil, 14784
Local Institution
Rio De Janeiro, Brazil, 20231
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Local Institution
London, Ontario, Canada, N6A 4L6
Canada, Quebec
Centre De Sante Et De Services Sociaux Rimouski Neigette
Rimouski, Quebec, Canada, G5L 5T1
Chile
Local Institution
Santiago, Metropolitana, Chile, 7600448
Local Institution
Santiago, Metropolitana, Chile
Local Institution
Recoleta, Santiago de Chile, Chile
Local Institution
Vi?a Del Mar, Valparaiso, Chile
Czech Republic
Local Institution
Praha 8, Czech Republic, 180 81
France
Local Institution
Creteil, France, 94010
Local Institution
Dijon Cedex, France, 21079
Local Institution
La Roche Sur Yon Cedex 9, France, 85925
Local Institution
Lyon Cedex 08, France, 69373
Local Institution
Marseille Cedex 20, France, 13915
Local Institution
Poitiers, France, 86000
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Rennes Cedex 9, France, 35033
Local Institution
Toulouse, France, 31300
Germany
Local Institution
Bad Berka, Germany, 99437
Local Institution
Gerlingen, Germany, 70839
Local Institution
Grosshansdorf, Germany, 22927
Local Institution
Heidelberg, Germany, 69126
Local Institution
Koeln, Germany, 51109
Local Institution
Mainz, Germany, 55131
Local Institution
Recklinghausen, Germany, 45657
Local Institution
Ulm, Germany, 89081
Hong Kong
Local Institution
Hong Kong, Hong Kong
Hungary
Local Institution
Budapest, Hungary, H-1121
Italy
Local Institution
Bergamo, Italy, 24127
Local Institution
Bologna, Italy, 40138
Local Institution
Meldola (fc), Italy, 47014
Local Institution
Milano, Italy, 20133
Local Institution
Padova, Italy, 35128
Local Institution
Parma, Italy, 43100
Local Institution
Perugia, Italy, 06132
Local Institution
Ravenna, Italy, 48100
Local Institution
Siena, Italy, 53100
Mexico
Local Institution
Mexico City, Distrito Federal, Mexico, 14080
Local Institution
Mexico, Distrito Federal, Mexico, 06735
Local Institution
Monterrey, Nuevo Leon, Mexico, 64060
Local Institution
Hermosillo, Sonora, Mexico, 83280
Norway
Local Institution
Oslo, Norway, 0424
Peru
Local Institution
Miraflores, Lima, Peru, 18
Local Institution
Arequipa, Peru, 54
Local Institution
Lima, Peru, 34
Local Institution
Lima, Peru, L-27
Poland
Local Institution
Gdansk, Poland, 80-19
Local Institution
Krakow, Poland, 31-202
Local Institution
Olsztyn, Poland, 10-513
Local Institution
Szczecin, Poland, 70891
Local Institution
Warszawa, Poland, 02-781
Romania
Local Institution
Bucuresti, Romania, 010976
Local Institution
Cluj-Napoca, Romania, 400352
Local Institution
Craiova, Romania, 200385
Local Institution
Iasi, Romania, 700106
Local Institution
Timisoara, Romania, 300167
Russian Federation
Local Institution
Moscow, Russian Federation, 115 478
Local Institution
Moscow, Russian Federation, 129128
Local Institution
St. Petersburg, Russian Federation, 197022
Singapore
Local Institution
Singapore, Singapore, 169610
Local Institution
Singapore, Singapore, 308433
Spain
Local Institution
Barcelona, Spain, 08035
Local Institution
Madrid, Spain, 28040
Local Institution
Madrid, Spain, 28050
Local Institution
Sevilla, Spain, 41013
Local Institution
Vizcaya, Spain, 48903
Switzerland
Local Institution
Chur, Graubuenden, Switzerland, 7000
Local Institution
Basel, Switzerland, 4031
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01673867     History of Changes
Other Study ID Numbers: CA209-057  2012-002472-14 
Study First Received: August 24, 2012
Results First Received: January 29, 2016
Last Updated: July 18, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Brazil: National Health Surveillance Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Mexico: Federal Commission for Sanitary Risks Protection
Norway: Data Protection Authority
Norway: Directorate of Health
Peru: Instituto Nacional de Salud
Poland: National Institute of Medicines
Romania: National Medicines Agency
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Federal Office of Public Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016