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An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026)

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ClinicalTrials.gov Identifier: NCT02041533
Recruitment Status : Active, not recruiting
First Posted : January 22, 2014
Results First Posted : July 26, 2017
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The purpose of this study is to show that Nivolumab will improve progression free survival in subjects with strongly Stage IV or Recurrent PD-L1+ non-small cell lung cancer when compared to chemotherapy

Condition or disease Intervention/treatment Phase
Stage IV or Recurrent Non-Small Cell Lung Cancer Biological: Nivolumab Drug: Gemcitabine Drug: Cisplatin Drug: Carboplatin Drug: Paclitaxel Drug: Pemetrexed Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1325 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer
Actual Study Start Date : March 25, 2014
Actual Primary Completion Date : July 1, 2016
Estimated Study Completion Date : October 1, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Arm A: Nivolumab subjects
Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure
Biological: Nivolumab
Other Names:
  • BMS-936558
  • MDX-1106

Active Comparator: Arm B: Investigator's Choice Chemotherapy

Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first

Squamous subjects:

  • Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or
  • Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or
  • Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle

Non-Squamous subjects:

  • Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle
  • Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle

Optional crossover:

  • Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure
Biological: Nivolumab
Other Names:
  • BMS-936558
  • MDX-1106

Drug: Gemcitabine
Other Name: Gemzar

Drug: Cisplatin
Other Name: Platinol

Drug: Carboplatin
Other Name: Paraplatin

Drug: Paclitaxel
Other Name: Taxol

Drug: Pemetrexed
Other Name: Alimta




Primary Outcome Measures :
  1. Progression-Free Survival in Participants With PD-L1 Expression >= 5% [ Time Frame: From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months) ]
    Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.


Secondary Outcome Measures :
  1. Progression-Free Survival in All Randomized Participants [ Time Frame: From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months) ]
    Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.

  2. Overall Survival in Participants With PD-L1 Expression >= 5% [ Time Frame: From date of randomization to date of death (assessed up to August 2016, approximately 28 months) ]
    Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.

  3. Overall Survival in All Randomized Participants [ Time Frame: From date of randomization to date of death (assessed up to August 2016, approximately 28 months) ]
    Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.

  4. Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5% [ Time Frame: From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to August 2016, approximately 28 months) ]
    ORR was defined as the proportion of randomized participants who achieved a Best Overall Response (BOR) of CR or PR using the RECIST v1.1 criteria per Independent Radiology Review Committee (IRRC) assessment. BOR was defined as the best response designation recorded between the date of randomization and the date of objectively documented progression or start of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. For participants who continued treatment beyond progression, BOR was determined from response designations recorded up to the time of initial progression. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir.

  5. Duration of Response in Participants With PD-L1 Expression>= 5% [ Time Frame: From date of first confirmed response to date of tumor progression (Assessed up to August 2016, approximately 28 months) ]
    Duration of Response (DOR) was summarized for participants with objective response and was defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression as determined by IRRC assessment (per RECIST v1.1) or death due to any cause, whichever occurs first. DOR censoring rules were the same as the PFS primary definition. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir

  6. Time to Response in Participants With PD-L1 Expression >= 5% [ Time Frame: From date of randomization to date of first confirmed response (assessed up to August 2016, approximately 18 months) ]
    Time to Response (TTR) was defined as the time from randomization to the date of the first response (CR or PR), as assessed by IRRC assessment. TTR was evaluated for responders only. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir.

  7. Disease-related Symptom Improvement Rate by Week 12 [ Time Frame: From date of randomization to week 12 ]
    The Lung Cancer Symptom Score (LCSS) is a validated instrument designed to assess the impact of treatment on disease-related symptoms. It consists of 6 symptom-specific questions related to dyspnea, cough, fatigue, pain, hemoptysis and anorexia plus 3 summary items: symptom distress, interference with activity, and global HRQoL. The degree of impairment was recorded on a 100 mm visual analogue scale with scores from 0 to 100 with zero representing the best score. Disease-related symptom improvement rate by Week 12 is defined as the proportion of all randomized (all PD-L1+) participants who had 10 points or more decrease from baseline in average symptom burden index score at any time between randomization and Week 12.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1
  • Histologically confirmed Stage IV, or Recurrent NSCLC with no prior systemic anticancer therapy
  • Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria
  • PD-L1+ on immunohistochemistry testing performed by central lab
  • Men and women, ages ≥ 18 years of age

Exclusion Criteria:

  • Known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy
  • Known anaplastic lymphoma kinase (ALK) translocations
  • Untreated central nervous system (CNS) metastases
  • Previous malignancies
  • Active, known or suspected autoimmune disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02041533


  Hide Study Locations
Locations
United States, Alabama
Southern Cancer Center, Inc.
Mobile, Alabama, United States, 36608
United States, Arizona
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
Arizona Oncol Assoc Dba (Hem Onc Physicians&Extenders) Hope
Tucson, Arizona, United States, 85704
United States, California
Stanford Cancer Institute
Stanford, California, United States, 94305-5826
United States, Colorado
University Of Colorado Hosp
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Florida
Baptist Health Medical Group Oncology
Miami, Florida, United States, 33176
Ocala Oncology Center
Ocala, Florida, United States, 34471
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University - Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Northwest Georgia Oncology Center, P.C.
Marietta, Georgia, United States, 30060
United States, Illinois
Rush University Med Ctr
Chicago, Illinois, United States, 60612-3841
United States, Kentucky
Baptist Health Lexington
Lexington, Kentucky, United States, 40503
United States, Louisiana
Crescent City Research Consortium, LLC
Marrero, Louisiana, United States, 70072
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center.
Boston, Massachusetts, United States, 02215
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
New York University Clinical Cancer Center
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
University Of North Carolina At Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7305
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospitals
Cleveland, Ohio, United States, 44106
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Lehigh Valley Health Network
Allentown, Pennsylvania, United States, 18103
University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
UPMC Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Hollings Cancer Center
Charleston, South Carolina, United States, 29425
St Francis Hospital
Greenville, South Carolina, United States, 29601
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-6307
United States, Texas
University Of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Univ Of Tx. Md Anderson
Houston, Texas, United States, 77030
Cancer Centers of South Texas
San Antonio, Texas, United States, 78212
United States, Washington
Yakima Valley Memorial Hospital/North Star Lodge
Yakima, Washington, United States, 98902
Argentina
COIBA
Berazategui, Buenos Aires, Argentina, 1880
Instituto Medico Especializado Alexander Fleming
Capital Federal, Buenos Aires, Argentina, 1426
Hospital Italiano De Buenos Aires
Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, 1181
Clinica Colombo
Cordoba, Argentina, 5000
Instituto Oncologico De Cordoba
Cordoba, Argentina, 5000
Australia, New South Wales
Local Institution
Camperdown, New South Wales, Australia, 2050
Australia, Queensland
Local Institution
Brisbane, Queensland, Australia, 4102
Australia, South Australia
Local Institution
Elizabeth Vale, South Australia, Australia, 5112
Australia, Victoria
Local Institution
Fitzroy, Victoria, Australia, 3065
Local Institution
Heidelberg, Victoria, Australia, 3084
Austria
Local Institution
Wels, Austria, 4600
Local Institution
Wien, Austria, 1090
Belgium
Universitair Ziekenhuis Brussel
Brussels, Belgium, 1090
Antwerp University Hospital
Edegem, Belgium, 2650
Uz Gent
Gent, Belgium, 9000
Uz Leuven
Leuven, Belgium, 3000
Brazil
Local Institution
Ijui, RIO Grande DO SUL, Brazil, 98700-000
Local Institution
Porto Alegre, RIO Grande DO SUL, Brazil, 90610-000
Local Institution
Barretos, SAO Paulo, Brazil, 14780-070
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Centre Hospitalier De L'Universite De Montreal
Montreal, Quebec, Canada, H2X 3E4
CISSS du Bas-Saint-Laurent Hopital Regional de Rimouski
Rimouski, Quebec, Canada, G5L 5T1
Czechia
Local Institution
Olomouc, Czechia, 779 00
Local Institution
Ostrava - Poruba, Czechia, 708 52
Local Institution
Praha 8, Czechia, 180 81
Local Institution
Usti nad Labem, Czechia, 401 13
Finland
Local Institution
Helsinki, Finland, 00029
Local Institution
Tampere, Finland, 33521
Local Institution
Vaasa, Finland, 65130
France
Local Institution
Caen, France, 14000
Local Institution
Lille, France, 59000
Local Institution
Marseille Cedex 20, France, 13915
Local Institution
Pontoise Cedex, France, 95303
Local Institution
Rennes Cedex 9, France, 35033
Local Institution
Strasbourg, France, 67090
Germany
Sozialstiftung Bamberg
Bamberg, Germany, 96049
Klinik Schillerhoehe
Gerlingen, Germany, 70839
Krankenhaus Grosshansdorf
Grosshansdorf, Germany, 22927
Thoraxklinik-Heidelberg Ggmbh
Heidelberg, Germany, 69126
Local Institution
Koeln, Germany, 50937
Local Institution
Wiesbaden, Germany, 65199
Greece
Local Institution
Heraklion, Creta, Greece, 71110
Local Institution
Athens, Greece, 11527
Hungary
Local Institution
Budapest, Hungary, 1121
Local Institution
Debrecen, Hungary, 4032
Local Institution
Matrahaza, Hungary, 3233
Italy
Azienda Ospedaliera Moscati
Avellino, Italy, 83100
Local Institution
Livorno, Italy, 57100
Local Institution
Milano, Italy, 20141
Local Institution
Napoli, Italy, 80131
Local Institution
Perugia, Italy, 06132
Local Institution
Terni, Italy, 05100
Japan
Local Institution
Nagoya-shi, Aichi, Japan, 4600001
Local Institution
Nagoya, Aichi, Japan, 4648681
Local Institution
Matsuyama-shi, Ehime, Japan, 7910280
Local Institution
Natori-shi, Miyagi, Japan, 9811293
Local Institution
Niigata-shi, Niigata, Japan, 9518566
Local Institution
Osaka-sayama, Osaka, Japan, 589-8511
Local Institution
Osaka-shi, Osaka, Japan, 5340021
Local Institution
Sakai-shi, Osaka, Japan, 591-8555
Local Institution
Kitaadachi-gun, Saitama, Japan, 3620806
Local Institution
Sunto-gun, Shizuoka, Japan, 4118777
Local Institution
Chuo-ku, Tokyo, Japan, 1040045
Local Institution
Akashi, Hyogo, Japan, 673-8558
Local Institution
Habikino City, Osaka, Japan, 5838588
Local Institution
Kobe, Hyogo, Japan, 6500047
Local Institution
Ota, Gunma, Japan, 3738550
Local Institution
Sapporo, Hokkaido, Japan, 062-0931
Local Institution
Tokyo, Japan, 1358550
Local Institution
Wakayama, Japan, 641-8510
Korea, Republic of
Local Institution
Seoul, Korea, Republic of, 120-752
Local Institution
Seoul, Korea, Republic of, 135-710
Local Institution
Seoul, Korea, Republic of
Mexico
Local Institution
Mexico City, Distrito Federal, Mexico, 14080
Local Institution
Guadalajara, Jalisco, Mexico, 44280
Local Institution
Merida, Yucatan, Mexico, 97133
Netherlands
Antoni Van Leeuwenhoek Ziekenhuis
Amsterdam, Netherlands, 1066 CX
Umcg, Universitair Medisch Centrum Groningen
Groningen, Netherlands, 9713 GZ
Local Institution
Rotterdam, Netherlands, 3015 CE
Poland
Local Institution
Bydgoszcz, Poland, 85-796
Local Institution
Krakow, Poland, 31-202
Local Institution
Lodz, Poland, 93-513
Local Institution
Warszawa, Poland, 02-781
Local Institution
Wodzislaw Slaski, Poland, 44-300
Romania
Local Institution
Cluj Napoca, Romania, 400015
Local Institution
Cluj-napoca, Romania, 400352
Local Institution
Ploiesti, Romania, 100337
Spain
Local Institution
Barcelona, Spain, 08035
Local Institution
Las Palmas De Gran Canaria, Spain, 35016
Local Institution
Madrid, Spain, 28050
Local Institution
Malaga, Spain, 29010
Local Institution
Sevilla, Spain, 41013
Local Institution
Valencia, Spain, 46014
Sweden
Local Institution
Stockholm, Sweden, 171 76
Local Institution
Uppsala, Sweden, 751 85
Switzerland
Local Institution
Chur, Switzerland, 7000
Local Institution
Lausanne, Switzerland, 1011
Local Institution
Zuerich, Switzerland, 8091
Taiwan
Local Institution
Taipei, Taiwan, 11217
Turkey
Local Institution
Kayseri, Turkey, 38039
United Kingdom
North Middlesex University Hospital
London, Greater London, United Kingdom, N18 1QX
Christie Hospital Nhs Trust
Manchester, Greater Manchester, United Kingdom, M20 4XB
St James'S University Hospital
Leeds, Yorkshire, United Kingdom, LS9 7TF
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02041533     History of Changes
Other Study ID Numbers: CA209-026
2012-004502-93 ( EudraCT Number )
First Posted: January 22, 2014    Key Record Dates
Results First Posted: July 26, 2017
Last Update Posted: February 14, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Paclitaxel
Gemcitabine
Nivolumab
Cisplatin
Carboplatin
Pemetrexed
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors