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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Mesothelioma

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Ipilimumab
* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab and Ipilimumab<br>Specified dose on specified days | Biological: Nivolumab<br> <br> * Other names: Opdivo;Biological: Ipilimumab<br> <br> * Other names: Yervoy;|
| Active Comparator: Pemetrexed and Cisplatin (or Carboplatin)<br>Specified dose on specified days | Drug: Pemetrexed<br> <br> Drug: Cisplatin<br> <br> Drug: Carboplatin<br> <br> |

What is the study measuring?
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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 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). | Up to 40 months | 
| Disease Control Rate (DCR) | 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). | Up to 40 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. | Up to 40 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. | Up to 40 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. | Up to 40 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. | Up to 40 months |