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)

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

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

Study Overview

• Status: Completed
• Conditions: Stage IV or Recurrent Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cisplatin; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Biological: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 541
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • Local Institution - 0050
  • Cordoba, Argentina, 5000
    • Local Institution - 0048
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, 1880
      • Local Institution - 0051
    • Capital Federal, Buenos Aires, Argentina, 1426
      • Local Institution - 0049
    • Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, 1181
      • Local Institution - 0052
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Local Institution - 0090
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Local Institution - 0091
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Local Institution - 0071
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Local Institution - 0072
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0104
• Austria
  • Wels, Austria, 4600
    • Local Institution - 0088
  • Wien, Austria, 1090
    • Local Institution - 0087
• Belgium
  • Brussels, Belgium, 1090
    • Local Institution - 0044
  • Edegem, Belgium, 2650
    • Local Institution - 0055
  • Gent, Belgium, 9000
    • Local Institution - 0056
  • Leuven, Belgium, 3000
    • Local Institution - 0062
• Brazil
  • Rio Grande Do Sul
    • Ijui, Rio Grande Do Sul, Brazil, 98700-000
      • Local Institution - 0134
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Local Institution - 0133
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14780-070
      • Local Institution - 0135
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Local Institution - 0086
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Local Institution - 0115
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0113
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Local Institution - 0110
    • Rimouski, Quebec, Canada, G5L 5T1
      • Local Institution - 0109
• Czechia
  • Olomouc, Czechia, 779 00
    • Local Institution - 0059
  • Ostrava - Poruba, Czechia, 708 52
    • Local Institution - 0061
  • Praha 8, Czechia, 180 81
    • Local Institution - 0058
  • Usti nad Labem, Czechia, 401 13
    • Local Institution - 0060
• Finland
  • Helsinki, Finland, 00029
    • Local Institution - 0120
  • Tampere, Finland, 33521
    • Local Institution - 0119
  • Vaasa, Finland, 65130
    • Local Institution - 0118
• France
  • Caen, France, 14000
    • Local Institution - 0123
  • Lille, France, 59000
    • Local Institution - 0105
  • Marseille Cedex 20, France, 13915
    • Local Institution - 0102
  • Pontoise Cedex, France, 95303
    • Local Institution - 0167
  • Rennes Cedex 9, France, 35033
    • Local Institution - 0100
  • Strasbourg, France, 67090
    • Local Institution - 0140
• Germany
  • Bamberg, Germany, 96049
    • Local Institution - 0074
  • Grosshansdorf, Germany, 22927
    • Local Institution - 0065
  • Heidelberg, Germany, 69126
    • Local Institution - 0064
  • Koeln, Germany, 50937
    • Local Institution - 0063
  • Stuttgart, Germany, 70376
    • Local Institution - 0066
  • Wiesbaden, Germany, 65199
    • Local Institution - 0092
• Greece
  • Athens, Greece, 11527
    • Local Institution - 0075
  • Creta
    • Heraklion, Creta, Greece, 71110
      • Local Institution - 0073
• Hungary
  • Budapest, Hungary, 1121
    • Local Institution - 0126
  • Debrecen, Hungary, 4032
    • Local Institution - 0116
  • Matrahaza, Hungary, 3233
    • Local Institution - 0094
• Italy
  • Avellino, Italy, 83100
    • Local Institution - 0084
  • Livorno, Italy, 57100
    • Local Institution - 0079
  • Milano, Italy, 20141
    • Local Institution - 0143
  • Napoli, Italy, 80131
    • Local Institution - 0142
  • Perugia, Italy, 06132
    • Local Institution - 0083
  • Terni, Italy, 05100
    • Local Institution - 0082
• Japan
  • Akashi, Hyogo, Japan, 673-8558
    • Local Institution - 0159
  • Ota, Gunma, Japan, 3738550
    • Local Institution - 0162
  • Sapporo, Hokkaido, Japan, 062-0931
    • Local Institution - 0165
  • Tokyo, Japan, 1358550
    • Local Institution - 0160
  • Wakayama, Japan, 641-8510
    • Local Institution - 0158
  • Aichi
    • Nagoya, Aichi, Japan, 4600001
      • Local Institution - 0146
    • Nagoya-shi, Aichi, Japan, 4640021
      • Local Institution - 0161
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 7910280
      • Local Institution - 0148
  • Hyogo
    • Kobe City, Hyogo, Japan, 6500047
      • Local Institution - 0153
  • Miyagi
    • Natori-shi, Miyagi, Japan, 9811293
      • Local Institution - 0144
  • Niigata
    • Niigata-shi, Niigata, Japan, 951-8566
      • Local Institution - 0151
  • Osaka
    • Habikino-shi, Osaka, Japan, 5638588
      • Local Institution - 0166
    • Miyakojima-ku, Osaka, Japan, 534-0021
      • Local Institution - 0147
    • Osaka-sayama, Osaka, Japan, 589-8511
      • Local Institution - 0145
    • Sakai, Osaka, Japan, 591-8555
      • Local Institution - 0152
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 3620806
      • Local Institution - 0150
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 4118777
      • Local Institution - 0149
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 1040045
      • Local Institution - 0154
• Korea, Republic of
  • Gangnam-gu, Korea, Republic of, 06351
    • Local Institution - 0155
  • Seoul, Korea, Republic of, 03722
    • Local Institution - 0164
  • Seoul, Korea, Republic of
    • Local Institution - 0163
• Mexico
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 14080
      • Local Institution - 0117
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Local Institution - 0122
  • Yucatan
    • Merida, Yucatan, Mexico, 97133
      • Local Institution - 0124
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0045
  • Groningen, Netherlands, 9700RB
    • Local Institution - 0057
  • Rotterdam, Netherlands, 3014 GD
    • Local Institution - 0046
• Poland
  • Bydgoszcz, Poland, 85-796
    • Local Institution - 0114
  • Krakow, Poland, 31-202
    • Local Institution - 0131
  • Lodz, Poland, 93-513
    • Local Institution - 0139
  • Warszawa, Poland, 02-781
    • Local Institution - 0089
  • Wodzislaw Slaski, Poland, 44-300
    • Local Institution - 0093
• Romania
  • Cluj Napoca, Romania, 400015
    • Local Institution - 0068
  • Cluj-napoca, Romania, 400352
    • Local Institution - 0067
  • Ploiesti, Romania, 100337
    • Local Institution - 0069
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0040
  • Las Palmas De Gran Canaria, Spain, 35016
    • Local Institution - 0041
  • Madrid, Spain, 28050
    • Local Institution - 0047
  • Malaga, Spain, 29010
    • Local Institution - 0042
  • Sevilla, Spain, 41013
    • Local Institution - 0039
  • Valencia, Spain, 46014
    • Local Institution - 0043
• Sweden
  • Stockholm, Sweden, 171 76
    • Local Institution - 0127
  • Uppsala, Sweden, 751 85
    • Local Institution - 0125
• Switzerland
  • Chur, Switzerland, 7000
    • Local Institution - 0076
  • Lausanne, Switzerland, 1011
    • Local Institution - 0077
  • Zuerich, Switzerland, 8091
    • Local Institution - 0078
• Taiwan
  • Taipei, Taiwan, 11217
    • Local Institution - 0157
• Turkey
  • Kayseri, Turkey, 38039
    • Local Institution - 0130
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, N18 1QX
      • Local Institution - 0098
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4XB
      • Local Institution - 0097
  • Yorkshire
    • Leeds, Yorkshire, United Kingdom, LS9 7TF
      • Local Institution - 0053
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Southern Cancer Center, Inc.
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85704
      • Local Institution - 0034
  • California
    • Stanford, California, United States, 94305-5826
      • Local Institution - 0016
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University Of Colorado Hosp
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0020
  • Florida
    • Miami, Florida, United States, 33176
      • Local Institution - 0030
    • Ocala, Florida, United States, 34471
      • Local Institution - 0033
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 0010
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Center, P.C.
  • Illinois
    • Chicago, Illinois, United States, 60612-3841
      • Local Institution - 0037
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Local Institution - 0014
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Crescent City Research Consortium, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0024
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 0036
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0070
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Local Institution - 0005
    • New York, New York, United States, 10016
      • Local Institution - 0009
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7305
      • University of North Carolina At Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0003
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Local Institution - 0012
    • Columbus, Ohio, United States, 43210
      • Local Institution - 0027
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health & Science University
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 0007
    • Philadelphia, Pennsylvania, United States, 19111
      • Local Institution - 0002
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 0054
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0018
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Local Institution - 0011
    • Greenville, South Carolina, United States, 29601
      • Local Institution - 0038
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6307
      • Local Institution - 0008
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution - 0006
    • Houston, Texas, United States, 77030
      • Local Institution - 0023
    • San Antonio, Texas, United States, 78212
      • Cancer Centers of South Texas
  • Washington
    • Yakima, Washington, United States, 98902
      • Local Institution - 0029

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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	Drug: Gemcitabine; Other Names: Gemzar; Drug: Cisplatin; Other Names: Platinol; Drug: Pemetrexed; Other Names: Alimta; Drug: Carboplatin; Other Names: Paraplatin; Drug: Paclitaxel; Other Names: Taxol; Biological: Nivolumab; Other Names: BMS-936558; MDX-1106

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival in Participants With PD-L1 Expression >= 5%	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.	From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival in All Randomized Participants	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.	From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)
Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5%	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.	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)
Disease-related Symptom Improvement Rate by 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.	From date of randomization to week 12
Overall Survival in Participants With PD-L1 Expression >= 5%	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.	From date of randomization to date of death (up to approximately 89 months)
Overall Survival in All Randomized Participants	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.	From date of randomization to date of death (up to approximately 89 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd

Publications and helpful links

General Publications

• Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA; CheckMate 026 Investigators. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 22;376(25):2415-2426. doi: 10.1056/NEJMoa1613493.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): May 27, 2022

Study Registration Dates

• First Submitted: January 19, 2014
• First Submitted That Met QC Criteria: January 19, 2014
• First Posted (Estimate): January 22, 2014

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Disease Attributes; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Gemcitabine; Carboplatin; Paclitaxel; Nivolumab; Pemetrexed
• Other Study ID Numbers: CA209-026; 2012-004502-93 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No