An Investigational Immuno-therapy Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC) (CheckMate 227)

• ClinicalTrials.gov Identifier: NCT02477826
• Recruitment Status: Active, not recruiting
• First Posted: June 23, 2015
• Last Update Posted: January 8, 2024
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: June 18, 2015
• First Posted Date: June 23, 2015
• Last Update Posted Date: January 8, 2024
• Actual Study Start Date: August 5, 2015
• Estimated Primary Completion Date: August 29, 2024 (Final data collection date for primary outcome measure)

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

• Overall survival (OS) [ Time Frame: approximately 48 months ]
• Progression-free Survival (PFS) as determined by blinded independent central review (BICR) [ Time Frame: approximately 40 months ]

Original Primary Outcome Measures (submitted: June 18, 2015)

• Overall survival (OS) [ Time Frame: approximately 48 months ]
  OS of nivolumab monotherapy and nivolumab in combination with ipilimumab to platinum-doublet chemotherapy in subjects with advanced lung cancer
• Progression-free survival (PFS) [ Time Frame: approximately 40 months ]
  PFS of nivolumab monotherapy and nivolumab in combination with ipilimumab to platinum-doublet chemotherapy in subjects with advanced lung cancer

Current Secondary Outcome Measures (submitted: January 26, 2017)

• Objective response rate (ORR) [ Time Frame: Up to 48 months ]
  ORR of nivolumab monotherapy and nivolumab in combination with ipilimumab to platinum-doublet chemotherapy in subjects with advanced lung cancer
• Disease related symptom improvement as measured by the Lung Cancer Symptom Score (LCSS) in all subjects [ Time Frame: Up to 48 months ]
  Disease related symptom improvement assessed at each dosing for 6 months, then every 6 weeks while on treatment

Original Secondary Outcome Measures (submitted: June 18, 2015)

• Objective response rate (ORR) [ Time Frame: upto 48 months ]
  ORR of nivolumab monotherapy and nivolumab in combination with ipilimumab to platinum-doublet chemotherapy in subjects with advanced lung cancer
• Disease related symptom improvement as measured by the Lung Cancer Symptom Score (LCSS) in all subjects [ Time Frame: upto 48 months ]
  Disease related symptom improvement assessed at each dosing for 6 months, then every 6 weeks while on treatment

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

Descriptive Information

• Brief Title: An Investigational Immuno-therapy Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)
• Official Title: An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)
• Brief Summary: The purpose of this study is to show that Nivolumab, or Nivolumab plus Ipilimumab, or Nivolumab plus Platinum-Doublet Chemotherapy improves progression free survival and/or overall survival compared with chemotherapy in patients with advanced lung cancer.
• 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: Non-Small Cell Lung Cancer

Intervention

• Drug: Nivolumab
  Other Name: Opdivo
• Drug: Ipilimumab
  Other Name: Yervoy
• Drug: Carboplatin
• Drug: Cisplatin
• Drug: Gemcitabine
• Drug: Pemetrexed
• Drug: Paclitaxel

Study Arms

• Experimental: Arm A: Nivolumab
  Nivolumab intravenously (IV) as specified
  Intervention: Drug: Nivolumab
• Experimental: Arm B: Nivolumab + Ipilimumab
  Nivolumab + Ipilimumab IV as specified
  Interventions:

  • Drug: Nivolumab
  • Drug: Ipilimumab
• Experimental: Arm C: Nivolumab + Platinum doublet chemotherapy
  Nivolumab + Platinum doublet chemotherapy (IV) dose as specified
  Interventions:

  • Drug: Nivolumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Gemcitabine
  • Drug: Pemetrexed
  • Drug: Paclitaxel
• Experimental: Arm D: Platinum doublet chemotherapy
  Chemotherapy administered on specified days of IV chemotherapy
  Interventions:

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

Publications *

• Reck M, Ciuleanu TE, Lee JS, Schenker M, Audigier-Valette C, Zurawski B, Linardou H, Otterson GA, Salman P, Nishio M, de la Mora Jimenez E, Lesniewski-Kmak K, Albert I, Ahmed S, Syrigos K, Penrod JR, Yuan Y, Blum SI, Nathan FE, Sun X, Moreno-Koehler A, Taylor F, O'Byrne KJ. First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1. J Thorac Oncol. 2021 Apr;16(4):665-676. doi: 10.1016/j.jtho.2020.12.019. Epub 2021 Jan 21.
• Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. doi: 10.1056/NEJMoa1910231. Epub 2019 Sep 28.
• Reck M, Schenker M, Lee KH, Provencio M, Nishio M, Lesniewski-Kmak K, Sangha R, Ahmed S, Raimbourg J, Feeney K, Corre R, Franke FA, Richardet E, Penrod JR, Yuan Y, Nathan FE, Bhagavatheeswaran P, DeRosa M, Taylor F, Lawrance R, Brahmer J. Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial. Eur J Cancer. 2019 Jul;116:137-147. doi: 10.1016/j.ejca.2019.05.008. Epub 2019 Jun 11.
• Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018 May 31;378(22):2093-2104. doi: 10.1056/NEJMoa1801946. Epub 2018 Apr 16.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 2, 2022): 2748
• Original Estimated Enrollment (submitted: June 18, 2015): 1980
• Estimated Study Completion Date: August 30, 2024
• Estimated Primary Completion Date: August 29, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy
• Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing, with results, performed by the central lab during the Screening period
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
• Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria

Exclusion Criteria:

• Subjects with untreated Central nervous system (CNS) metastases are excluded
• Subjects with an active, known or suspected autoimmune disease are excluded
• Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) indicating acute or chronic infection

Other protocol defined inclusion/exclusion criteria apply

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, Chile, China, Colombia, Czechia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lebanon, Mexico, Netherlands, Peru, Poland, Romania, Russian Federation, South Africa, Spain, Switzerland, Taiwan, United Kingdom, United States
• Removed Location Countries: Czech Republic, Saudi Arabia, Turkey, United Arab Emirates

Administrative Information

• NCT Number: NCT02477826
• Other Study ID Numbers: CA209-227; 2014-003630-23 ( 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: January 2024