Study of Nivolumab Combined With Ipilimumab Versus Pemetrexed and Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma Patients (CheckMate743)

• ClinicalTrials.gov Identifier: NCT02899299
• Recruitment Status: Completed
• First Posted: September 14, 2016
• Results First Posted: April 14, 2021
• Last Update Posted: July 5, 2023
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: August 31, 2016
• First Posted Date: September 14, 2016
• Results First Submitted Date: March 24, 2021
• Results First Posted Date: April 14, 2021
• Last Update Posted Date: July 5, 2023
• Actual Study Start Date: November 29, 2016
• Actual Primary Completion Date: March 25, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 24, 2021)

Overall Survival (OS) [ Time Frame: From randomization to the date of death (Up to 40 Months) ]

Overall Survival was defined as the time from randomization to the date of death due to any cause. A participant who has not died was censored at last known date alive.

Original Primary Outcome Measures (submitted: September 8, 2016)

• Overall Survival (OS) [ Time Frame: 3.5 years ]
• Progression Free Survival (PFS) [ Time Frame: 3.5 years ]

Current Secondary Outcome Measures (submitted: March 24, 2021)

• Objective Response Rate (ORR) [ Time Frame: Up to 40 months ]
  Objective Response Rate is defined as the percentage of randomized participants who achieve a best overall response of complete response or partial response per Blinded Independent Central Review (BICR) assessments (Per adapted m-RECIST for pleural mesothelioma and RECIST 1.1, confirmation of response required).
• Disease Control Rate (DCR) [ Time Frame: Up to 40 months ]
  Disease Control Rate is defined as the percentage of all randomized participants whose Best Overall Response was Complete Response, Partial Response, Stable Disease or Non-CR/Non-PD per adapted m-RECIST and RECIST 1.1 as assessed by Blinded Independent Central Review (BICR).
• Progression Free Survival (PFS) [ Time Frame: Up to 40 months ]
  Progression Free Survival is defined as the time between the date of randomization and the date of first documented tumor progression per Blinded Independent Central Review (BICR) assessments (using adapted m-RECIST and RECIST 1.1), or death due to any cause, whichever occurs first. Participants who received subsequent anticancer therapy prior to documented progression were censored at the date of the last evaluable tumor assessment conducted on or prior to the date of initiation of the subsequent anticancer therapy.
• Overall Survival (OS) According to PD-L1 Expression Level [ Time Frame: Up to 40 months ]
  PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by overall survival (OS) analysis.
• Progression Free Survival (PFS) According to PD-L1 Expression Level [ Time Frame: Up to 40 months ]
  PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by progression free survival (PFS) analysis.
• Objective Response Rate (ORR) According to PD-L1 Expression Level [ Time Frame: Up to 40 months ]
  PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by objective response rate (ORR) analysis.

Original Secondary Outcome Measures (submitted: September 8, 2016)

• Objective Response Rate (ORR) [ Time Frame: 3 years ]
• Disease Control Rate (DCR) [ Time Frame: 3 years ]
• Composite correlation of PD-L1 expression level and efficacy [ Time Frame: 3 years ]
  Efficacy determined by the ORR, PFS, and OS

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

Descriptive Information

• Brief Title: Study of Nivolumab Combined With Ipilimumab Versus Pemetrexed and Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma Patients
• Official Title: A Phase III, Randomized, Open Label Trial of Nivolumab in Combination With Ipilimumab Versus Pemetrexed With Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma
• Brief Summary: The purpose of this study is to test the effectiveness and tolerability of the combination of Nivolumab and Ipilimumab compared to Pemetrexed and Cisplatin or Carboplatin in patients with unresectable pleural mesothelioma.
• 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: Mesothelioma

Intervention

• Biological: Nivolumab
  Other Names:

  • BMS-936558
  • Opdivo
• Biological: Ipilimumab
  Other Names:

  • BMS-734016
  • Yervoy
• Drug: Pemetrexed
• Drug: Cisplatin
• Drug: Carboplatin

Study Arms

• Experimental: Nivolumab and Ipilimumab
  Specified dose on specified days
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
• Active Comparator: Pemetrexed and Cisplatin (or Carboplatin)
  Specified dose on specified days
  Interventions:

  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: Carboplatin

Publications *

• Scherpereel A, Antonia S, Bautista Y, Grossi F, Kowalski D, Zalcman G, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Sun X, Lawrance R, Zhang X, Daumont MJ, Bennett B, McKenna M, Baas P. First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743. Lung Cancer. 2022 May;167:8-16. doi: 10.1016/j.lungcan.2022.03.012. Epub 2022 Mar 21.
• Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, Talbot T, Monnet I, Hiret S, Baas P, Nowak AK, Fujimoto N, Tsao AS, Mansfield AS, Popat S, Zhang X, Hu N, Balli D, Spires T, Zalcman G. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022 May;33(5):488-499. doi: 10.1016/j.annonc.2022.01.074. Epub 2022 Feb 3.
• Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Jahan T, Antonia S, Oulkhouir Y, Bautista Y, Cornelissen R, Greillier L, Grossi F, Kowalski D, Rodriguez-Cid J, Aanur P, Oukessou A, Baudelet C, Zalcman G. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. doi: 10.1016/S0140-6736(20)32714-8. Epub 2021 Jan 21. Erratum In: Lancet. 2021 Feb 20;397(10275):670.
• Wright K. FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma. Oncology (Williston Park). 2020 Nov 12;34(11):502-503. doi: 10.46883/ONC.2020.3411.0502.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 2, 2020): 605
• Original Estimated Enrollment (submitted: September 8, 2016): 600
• Actual Study Completion Date: May 30, 2023
• Actual Primary Completion Date: March 25, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Males and Females at least 18 years of age
• Histologically confirmed pleural malignant mesothelioma not eligible for curative surgery
• ECOG Performance status of 0 or 1
• Available tumor sample for testing
• Acceptable blood work

Exclusion Criteria:

• Primitive peritoneal, pericardial and tunica vaginalis testis mesotheliomas
• Prior chemotherapy for pleural mesothelioma
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 oranti-CTLA-4 antibody
• History of other malignancy unless the subject has been disease-free for at least 3 years
• Active, untreated central nervous system (CNS) metastasis

Other protocol defined inclusion/exclusion criteria could 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: Australia, Belgium, Brazil, Chile, China, Colombia, France, Germany, Greece, Italy, Japan, Mexico, Netherlands, Poland, Romania, Russian Federation, South Africa, Switzerland, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT02899299
• Other Study ID Numbers: CA209-743; 2016-001859-43 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• 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: June 2023