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)

• ClinicalTrials.gov Identifier: NCT02041533
• Recruitment Status: Completed
• First Posted: January 22, 2014
• Results First Posted: July 26, 2017
• Last Update Posted: March 2, 2023
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: January 19, 2014
• First Posted Date: January 22, 2014
• Results First Submitted Date: June 26, 2017
• Results First Posted Date: July 26, 2017
• Last Update Posted Date: March 2, 2023
• Actual Study Start Date: March 27, 2014
• Actual Primary Completion Date: July 1, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 26, 2017)

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.

Original Primary Outcome Measures (submitted: January 19, 2014)

Progression Free Survival (PFS) as assessed by independent radiology review committee (IRRC) in subjects with strongly Programmed death-ligand 1+ (PD-L1+) tumor expression [ Time Frame: Up to approximately 33 months ]

PFS is defined as the time from randomization to the date of the first documented tumor progression as determined by the IRRC (per RECIST 1.1), or death due to any cause

Current Secondary Outcome Measures (submitted: February 2, 2023)

• 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.
• Overall Survival in Participants With PD-L1 Expression >= 5% [ Time Frame: From date of randomization to date of death (up to approximately 89 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.
• Overall Survival in All Randomized Participants [ Time Frame: From date of randomization to date of death (up to approximately 89 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: January 19, 2014)

• Objective response rate (ORR) as determined per IRRC in subjects with strongly PD-L1+ tumor expression [ Time Frame: Up to approximately 33 months ]
  ORR is defined as the number of subjects whose best confirmed objective response is a complete response (CR) or partial response (PR), divided by the number of randomized subjects among strongly PD-L1+ subjects
• Overall survival (OS) in subjects with strongly PD-L1+ tumor expression [ Time Frame: At least 33 months ]
  OS is defined as the time from randomization to the date of death
• PFS in all subjects with any PD-L1+ tumor expression [ Time Frame: Up to approximately 33 months ]
• Disease related symptom improvement in all subjects [ Time Frame: Up to approximately 33 months ]
  Disease-related symptom improvement rate is defined as the proportion of randomized subjects who had a disease-related symptom improvement as measured by the lung cancer symptom scale (LCSS) among all PD-L1+ subjects

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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 (CheckMate 026)
• 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Stage IV or Recurrent Non-Small Cell Lung Cancer

Intervention

• 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

Study Arms

• 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
  Intervention: Biological: Nivolumab
• 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
  Interventions:

  • Biological: Nivolumab
  • Drug: Gemcitabine
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Pemetrexed

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 2, 2023): 541
• Original Estimated Enrollment (submitted: January 19, 2014): 495
• Actual Study Completion Date: May 27, 2022
• Actual Primary Completion Date: July 1, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Finland, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02041533
• Other Study ID Numbers: CA209-026; 2012-004502-93 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Ono Pharmaceutical Co. Ltd

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: February 2023