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: Active, not recruiting
• First Posted: September 14, 2016
• Results First Posted: April 14, 2021
• Last Update Posted: March 15, 2023
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mesothelioma	Biological: Nivolumab; Biological: Ipilimumab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin	Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 605 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 29, 2016
• Actual Primary Completion Date: March 25, 2020
• Estimated Study Completion Date: April 28, 2023

Arms and Interventions

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: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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).
2. 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).
3. 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.
4. 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.
5. 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.
6. 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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

Ucsf

San Francisco, California, United States, 94143

United States, Connecticut

Local Institution - 0014

New Haven, Connecticut, United States, 06520

United States, Florida

H. Lee Moffitt Cancer Center & Research Inst, Inc

Tampa, Florida, United States, 33612

United States, Illinois

Local Institution - 0002

Chicago, Illinois, United States, 60637

United States, Maryland

Univ Of Maryland Greenbaum Cancer Center

Baltimore, Maryland, United States, 21201

United States, Michigan

Local Institution - 0013

Detroit, Michigan, United States, 48201

Cancer & Hematology Centers Of Western Michigan

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

Local Institution - 0004

Rochester, Minnesota, United States, 55905

United States, New York

Memorial Sloan Kettering Nassau

New York, New York, United States, 10065

United States, Ohio

Local Institution - 0007

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

University Of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Allegheny Cancer Center

Pittsburgh, Pennsylvania, United States, 15212

United States, Texas

Local Institution - 0005

Houston, Texas, United States, 77030

United States, West Virginia

West Virginia University

Morgantown, West Virginia, United States, 26506

Australia, New South Wales

Local Institution - 0032

Sydney, New South Wales, Australia, 2139

Australia, Queensland

Local Institution - 0031

Birtinya, Queensland, Australia, 4575

Australia, Victoria

Local Institution - 0033

Clayton, Victoria, Australia, 3168

Local Institution - 0030

Malvern, Victoria, Australia, 3144

Australia, Western Australia

Local Institution - 0034

Nedlands, Western Australia, Australia, 6009

Belgium

Local Institution - 0089

Brussels, Belgium, 1090

Local Institution - 0086

Edegem, Belgium, 2650

Local Institution - 0087

Liège, Belgium, 4000

Local Institution - 0088

Sint-Niklaas, Belgium, 9100

Brazil

Local Institution

Barretos, Sao Paulo, Brazil, 14784-400

Local Institution - 0064

Sao Paulo, Brazil, 05403-010

Chile

Local Institution - 0018

Santiago, Metropolitana, Chile, 8420383

China, Heilongjiang

Local Institution - 0133

Harbin Shi, Heilongjiang, China, 150081

China, Jilin

Local Institution

Changchun, Jilin, China, 130021

China, Liaoning

Local Institution

Shenyang, Liaoning, China

China

Local Institution - 0124

Kunming, China, 0

Local Institution - 0120

Shanghai, China, 200030

Colombia

Local Institution - 0039

Bogota, Colombia, 0

Local Institution - 0040

Bogota, Colombia, 0

France

Local Institution - 0057

Caen, France, 14033

Local Institution - 0073

Creteil, France, 94010

Local Institution - 0074

La Tronche, France, 38700

Local Institution - 0067

Lille Cedex, France, 59037

Local Institution - 0069

Marseille Cedex 20, France, 13915

Local Institution - 0056

Paris, France, 75018

Local Institution - 0080

Saint Herblain, France, 44805

Local Institution - 0093

Strasbourg Cedex, France, 67091

Local Institution - 0058

Toulon Cedex, France, 83056

Local Institution - 0068

Toulouse Cedex 9, France, 31059

Germany

Local Institution - 0026

Cologne, Germany, 51109

Local Institution - 0054

Coswig, Germany, 01640

Local Institution - 0038

Essen, Germany, 45147

Local Institution

Essen, Germany, 45147

Local Institution - 0023

Gottingen, Germany, 37075

Local Institution - 0024

Grosshansdorf, Germany, 22927

Local Institution - 0027

Hamburg, Germany, 21075

Local Institution - 0037

Heidelberg, Germany, 69126

Local Institution - 0021

Homburg an d. Saar, Germany, 66421

Local Institution - 0022

Immenhausen, Germany, 34376

Local Institution - 0019

Moers, Germany, 47441

Greece

Local Institution - 0017

Athens, Greece, 11527

Local Institution - 0016

Thessaloniki, Greece, 57001

Italy

Local Institution - 0042

Ravenna, Emilia-Romagna, Italy, 48121

Local Institution - 0047

Aviano, Italy, 33081

Local Institution - 0044

Bari, Italy, 70124

Local Institution - 0046

Catania, Italy, 95124

Local Institution - 0045

Genova, Italy, 16132

Local Institution - 0043

Napoli, Italy, 80131

Local Institution - 0048

Rozzano, Italy, 20089

Local Institution - 0041

Siena, Italy, 53100

Japan

Local Institution - 0105

Nagoya-shi, Aichi, Japan, 4668560

Local Institution - 0097

Chiba-shi, Chiba, Japan, 2608677

Local Institution - 0108

Fukuyama-shi, Hiroshima, Japan, 7200001

Local Institution - 0114

Hiroshima-Shi, Hiroshima, Japan, 7348551

Local Institution - 0101

Sapporo-shi, Hokkaido, Japan, 0030804

Local Institution - 0106

Amagasaki-shi, Hyogo, Japan, 6608550

Local Institution - 0098

Nishinomiya-shi, Hyogo, Japan, 6638501

Local Institution - 0095

Yokohama-shi, Kanagawa, Japan, 2210855

Local Institution - 0104

Natori-shi, Miyagi, Japan, 9811293

Local Institution - 0107

Niigata-shi, Niigata, Japan, 9518520

Local Institution - 0100

Okayama-shi, Okayama, Japan, 7028055

Local Institution - 0096

Kitaadachi-gun, Saitama, Japan, 3620806

Local Institution - 0094

Chuo-ku, Tokyo, Japan, 1040045

Local Institution - 0099

Ube-shi, Yamaguchi, Japan, 7550241

Local Institution - 0113

Osakasayama-city, Japan, 5898511

Mexico

Local Institution - 0079

Df, Distrito Federal, Mexico, 06720

Local Institution - 0053

Mexico, Distrito Federal, Mexico, 14000

Local Institution - 0050

Mexico, Distrito Federal, Mexico, 14050

Local Institution - 0051

Guadalajara, Jalisco, Mexico, 44270

Local Institution - 0118

Chihuahua, Mexico, 31000

Netherlands

Local Institution - 0092

Amsterdam, Netherlands, 1066 CX

Local Institution - 0091

Rotterdam, Netherlands, 3000 CA

Poland

Local Institution - 0078

Bytom, Poland, 41-902

Local Institution - 0076

Krakow, Poland, 31-202

Local Institution - 0077

Warszawa, Poland, 02-781

Romania

Local Institution - 0115

Bucharest, Romania, 020122

Local Institution - 0109

Bucuresti, Romania, 021389

Local Institution - 0102

Craiova, Romania, 200347

Local Institution - 0055

Romania, Romania, 400015

Russian Federation

Local Institution - 0150

Moscow, Russian Federation, 115478

Local Institution - 0071

Moscow, Russian Federation, 121309

Local Institution - 0072

Saint Petersburg, Russian Federation, 197758

South Africa

Local Institution - 0060

Pretoria, Gauteng, South Africa, 0075

Local Institution - 0059

Cape Town, Western Cape, South Africa, 7570

Switzerland

Local Institution - 0049

Bern, Bern (de), Switzerland, 3010

Local Institution - 0036

Lausanne, Switzerland, 1011

Local Institution - 0029

Zurich, Switzerland, 8091

Turkey

Local Institution - 0111

Diyarbakır, Turkey, 21280

Local Institution - 0112

Istanbul, Turkey, 34098

Local Institution - 0110

Seyhan, Turkey, 01130

United Kingdom

Local Institution - 0085

Truro, Cornwall, United Kingdom, TR1 3LJ

Local Institution - 0084

Edinburgh, Midlothian, United Kingdom, EH4 2XU

Local Institution - 0081

Leicester, United Kingdom, LE1 5WW

Local Institution - 0083

London, United Kingdom, EC1A 7BE

Local Institution - 0116

Manchester, United Kingdom, M23 9LT

Local Institution - 0090

Southampton, United Kingdom, SO16 6YD

Sponsors and Collaborators

Bristol-Myers Squibb

Ono Pharmaceutical Co. Ltd

Investigators

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

  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:

Study Protocol  [PDF] April 25, 2019

Statistical Analysis Plan  [PDF] November 7, 2019

More Information

Additional Information:

BMS Clinical Trial Information 

BMS Clinical Trial Patient Recruiting 

FDA Safety Alerts and Recalls 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02899299
• Other Study ID Numbers: CA209-743; 2016-001859-43 ( EudraCT Number )
• First Posted: September 14, 2016
• Results First Posted: April 14, 2021
• Last Update Posted: March 15, 2023
• Last Verified: February 2023

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; Nivolumab; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carboplatin; Pemetrexed; Ipilimumab; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors