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

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

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.

Study Overview

• Status: Completed
• Conditions: Mesothelioma
• Intervention / Treatment: Drug: Cisplatin; Drug: Pemetrexed; Drug: Carboplatin; Biological: Nivolumab; Biological: Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 605
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2139
      • Local Institution - 0032
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Local Institution - 0031
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 0033
    • Malvern, Victoria, Australia, 3144
      • Local Institution - 0030
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution - 0034
• Belgium
  • Brussels, Belgium, 1090
    • Local Institution - 0089
  • Edegem, Belgium, 2650
    • Local Institution - 0086
  • Liège, Belgium, 4000
    • Local Institution - 0087
  • Sint-Niklaas, Belgium, 9100
    • Local Institution - 0088
• Brazil
  • Sao Paulo, Brazil, 05403-010
    • Local Institution - 0064
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Local Institution
• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile, 8420383
      • Local Institution - 0018
• China
  • Kunming, China
    • Local Institution - 0124
  • Shanghai, China, 200030
    • Local Institution - 0120
  • Heilongjiang
    • Harbin Shi, Heilongjiang, China, 150081
      • Local Institution - 0133
  • Jilin
    • Changchun, Jilin, China, 130021
      • Local Institution
  • Liaoning
    • Shenyang, Liaoning, China
      • Local Institution
• Colombia
  • Bogota, Colombia
    • Local Institution - 0039
  • Bogota, Colombia
    • Local Institution - 0040
• France
  • Caen, France, 14033
    • Local Institution - 0057
  • Creteil, France, 94010
    • Local Institution - 0073
  • La Tronche, France, 38700
    • Local Institution - 0074
  • Lille Cedex, France, 59037
    • Local Institution - 0067
  • Marseille Cedex 20, France, 13915
    • Local Institution - 0069
  • Paris, France, 75018
    • Local Institution - 0056
  • Saint Herblain, France, 44805
    • Local Institution - 0080
  • Strasbourg Cedex, France, 67091
    • Local Institution - 0093
  • Toulon Cedex, France, 83056
    • Local Institution - 0058
  • Toulouse Cedex 9, France, 31059
    • Local Institution - 0068
• Germany
  • Cologne, Germany, 51109
    • Local Institution - 0026
  • Coswig, Germany, 01640
    • Local Institution - 0054
  • Essen, Germany, 45147
    • Local Institution - 0038
  • Gottingen, Germany, 37075
    • Local Institution - 0023
  • Grosshansdorf, Germany, 22927
    • Local Institution - 0024
  • Hamburg, Germany, 21075
    • Local Institution - 0027
  • Heidelberg, Germany, 69126
    • Local Institution - 0037
  • Homburg an d. Saar, Germany, 66421
    • Local Institution - 0021
  • Immenhausen, Germany, 34376
    • Local Institution - 0022
  • Moers, Germany, 47441
    • Local Institution - 0019
• Greece
  • Athens, Greece, 11527
    • Local Institution - 0017
  • Thessaloniki, Greece, 57001
    • Local Institution - 0016
• Italy
  • Aviano, Italy, 33081
    • Local Institution - 0047
  • Bari, Italy, 70124
    • Local Institution - 0044
  • Catania, Italy, 95124
    • Local Institution - 0046
  • Genova, Italy, 16132
    • Local Institution - 0045
  • Napoli, Italy, 80131
    • Local Institution - 0043
  • Rozzano, Italy, 20089
    • Local Institution - 0048
  • Siena, Italy, 53100
    • Local Institution - 0041
  • Emilia-Romagna
    • Ravenna, Emilia-Romagna, Italy, 48121
      • Local Institution - 0042
• Japan
  • Osakasayama-city, Japan, 5898511
    • Local Institution - 0113
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4668560
      • Local Institution - 0105
  • Chiba
    • Chiba-shi, Chiba, Japan, 2608677
      • Local Institution - 0097
  • Hiroshima
    • Fukuyama-shi, Hiroshima, Japan, 7200001
      • Local Institution - 0108
    • Hiroshima-Shi, Hiroshima, Japan, 7348551
      • Local Institution - 0114
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 0030804
      • Local Institution - 0101
  • Hyogo
    • Amagasaki-shi, Hyogo, Japan, 6608550
      • Local Institution - 0106
    • Nishinomiya-shi, Hyogo, Japan, 6638501
      • Local Institution - 0098
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan, 2210855
      • Local Institution - 0095
  • Miyagi
    • Natori-shi, Miyagi, Japan, 9811293
      • Local Institution - 0104
  • Niigata
    • Niigata-shi, Niigata, Japan, 9518520
      • Local Institution - 0107
  • Okayama
    • Okayama-shi, Okayama, Japan, 7028055
      • Local Institution - 0100
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 3620806
      • Local Institution - 0096
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 1040045
      • Local Institution - 0094
  • Yamaguchi
    • Ube-shi, Yamaguchi, Japan, 7550241
      • Local Institution - 0099
• Mexico
  • Chihuahua, Mexico, 31000
    • Local Institution - 0118
  • Distrito Federal
    • Df, Distrito Federal, Mexico, 06720
      • Local Institution - 0079
    • Mexico, Distrito Federal, Mexico, 14000
      • Local Institution - 0053
    • Mexico, Distrito Federal, Mexico, 14050
      • Local Institution - 0050
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44270
      • Local Institution - 0051
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0092
  • Rotterdam, Netherlands, 3000 CA
    • Local Institution - 0091
• Poland
  • Bytom, Poland, 41-902
    • Local Institution - 0078
  • Krakow, Poland, 31-202
    • Local Institution - 0076
  • Warszawa, Poland, 02-781
    • Local Institution - 0077
• Romania
  • Bucharest, Romania, 020122
    • Local Institution - 0115
  • Bucuresti, Romania, 021389
    • Local Institution - 0109
  • Craiova, Romania, 200347
    • Local Institution - 0102
  • Romania, Romania, 400015
    • Local Institution - 0055
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Local Institution - 0150
  • Moscow, Russian Federation, 121309
    • Local Institution - 0071
  • Saint Petersburg, Russian Federation, 197758
    • Local Institution - 0072
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0075
      • Local Institution - 0060
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7570
      • Local Institution - 0059
• Switzerland
  • Bern, Switzerland, 3010
    • Local Institution - 0049
  • Lausanne, Switzerland, 1011
    • Local Institution - 0036
  • Zurich, Switzerland, 8091
    • Local Institution - 0029
• Turkey
  • Diyarbakır, Turkey, 21280
    • Local Institution - 0111
  • Istanbul, Turkey, 34098
    • Local Institution - 0112
  • Seyhan, Turkey, 01130
    • Local Institution - 0110
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Local Institution - 0081
  • London, United Kingdom, EC1A 7BE
    • Local Institution - 0083
  • Manchester, United Kingdom, M23 9LT
    • Local Institution - 0116
  • Southampton, United Kingdom, SO16 6YD
    • Local Institution - 0090
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Local Institution - 0085
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH4 2XU
      • Local Institution - 0084
• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0014
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Inst, Inc
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Local Institution - 0002
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ Of Maryland Greenbaum Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Local Institution - 0013
    • Grand Rapids, Michigan, United States, 49503
      • Cancer & Hematology Centers of Western Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 0004
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Nassau
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 0007
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Local Institution - 0005
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

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

Description

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

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: Nivolumab and Ipilimumab; Specified dose on specified days	Biological: Nivolumab; Other Names: BMS-936558; Opdivo; Biological: Ipilimumab; Other Names: BMS-734016; Yervoy
Active Comparator: Pemetrexed and Cisplatin (or Carboplatin); Specified dose on specified days	Drug: Cisplatin; Drug: Pemetrexed; Drug: Carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	From randomization to the date of death (Up to 40 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate is defined as the percentage of randomized participants who achieve a best overall response of complete response (CR) or partial response (PR) per Blinded Independent Central Review (BICR) assessments. Per adapted m-RECIST for pleural mesothelioma, each single tumor measurement must be at least 10 mm in length to qualify as measureable disease and contribute to the sum that defines the pleural uni-variate measure. Per RECIST 1.1 for solid tumors, confirmation of response required: CR=Disappearance of all target lesions; PR=At least a 30% decrease in the sum of the Total Tumor Measurement; Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement.	From randomization date to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (Up to 76 months)
Disease Control Rate (DCR)	Disease Control Rate is defined as the percentage of all randomized participants whose Best Overall Response was complete response (CR), partial response (PR), stable disease (SD) or Non-CR/Non-PD as assessed by Blinded Independent Central Review (BICR). Per adapted m-RECIST for pleural mesothelioma, each single tumor measurement must be at least 10 mm in length to qualify as measureable disease and contribute to the sum that defines the pleural uni-variate measure. Per RECIST 1.1 for solid tumors, confirmation of response required: CR=Disappearance of all target lesions; PR=At least a 30% decrease in the sum of the Total Tumor Measurement; Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement; SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Non-CR/Non-PD: Persistence of one or more non-target lesion(s).	From randomization date to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (Up to 76 months
Progression Free Survival (PFS)	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. Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement.	From randomization date to the date of first documented tumor progression or death due to any cause, whichever occurs first. (up to 76 months)
Overall Survival (OS) According to PD-L1 Expression Level	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. OS 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.	From randomization date to the date of death (Up to 76 Months)
Progression Free Survival (PFS) According to PD-L1 Expression Level	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. PFS 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. Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement.	From randomization date to the date of first documented tumor progression or death due to any cause, whichever occurs first. (up to 76 months)
Objective Response Rate (ORR) According to PD-L1 Expression Level	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. ORR is defined as the percentage of participants who achieve a best overall response of complete response (CR) or partial response (PR) per Blinded Independent Central Review (BICR) assessments. Per adapted m-RECIST for pleural mesothelioma, each single tumor measurement must be at least 10 mm in length to qualify as measureable disease and contribute to the sum that defines the pleural uni-variate measure. per RECIST 1.1 for solid tumors, confirmation of response required: CR=Disappearance of all target lesions; PR=At least a 30% decrease in the sum of the Total Tumor Measurement; Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement.	From randomization date to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (Up to 76 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2016
• Primary Completion (Actual): March 25, 2020
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: August 31, 2016
• First Submitted That Met QC Criteria: September 8, 2016
• First Posted (Estimated): September 14, 2016

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Nivolumab; Pemetrexed; Ipilimumab
• Other Study ID Numbers: CA209-743; 2016-001859-43 (EudraCT Number)