A Study of Pembrolizumab in Combination With Cisplatin and Pemetrexed in Advanced Malignant Pleural Mesothelioma (MPM) (MK-3475-A17)

Study Overview
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Brief Summary
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This is a multicenter, open-label, non-randomized, study of pembrolizumab in combination with cisplatin and pemetrexed in treatment of naïve participants with a histologically confirmed diagnosis of advanced/unresectable malignant pleural mesothelioma (MPM) in Japanese participants. This study will evaluate the safety, tolerability, and preliminary efficacy of pembrolizumab in combination with cisplatin and pemetrexed. The primary objective is to evaluate the safety and tolerability of treatment with pembrolizumab in combination with cisplatin and pemetrexed.

Official Title
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A Phase Ib Clinical Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Cisplatin and Pemetrexed in Treatment-naive Participants With Advanced Malignant Pleural Mesothelioma (KEYNOTE-A17).

Conditions
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Mesothelioma

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Pemetrexed
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histologically confirmed diagnosis of advanced/unresectable malignant pleural mesothelioma (MPM) Have at least one measurable disease, which is systemic therapy naïve, radiologically assessed by the local site investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) using imaging scanned within 28 days prior to the first dose in this study Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale Has a life expectancy of at least 3 months Demonstrate adequate organ function Male participants are eligible to participate if they agree to remain abstinent or agree to use contraception unless confirmed to be azoospermic A female participant is eligible to participate if she is not pregnant or breastfeeding, using contraceptives or is not a woman of child bearing potential (WOCBP) Exclusion Criteria: A WOCBP who has a positive pregnancy test within 72 hours prior to treatment allocation Has received prior therapy with an anti-programmed cell-death 1 (anti PD-1), anti programmed cell-death ligand 1 (anti-PD-L1), or anti programmed cell-death ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor Has previously received systemic anti-cancer therapy (including investigational agents) for MPM Participants who received (neo) adjuvant previously may be eligible, only if the last dose of chemotherapy was completed at least 6 months before registration. Such participants must have recovered from all adverse events (AEs) due to previous (neo) adjuvant therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible Received radiation therapy to the lung that is > 30 gray (Gy) within 6 months of the first dose of trial treatment Completed palliative radiotherapy within 7 days of the first dose of trial treatment Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis Had a major surgery within 3 months prior to the first administration in this study Has received a live vaccine within 30 days prior to the first dose of study drug Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis Has had a severe hypersensitivity reaction (≥Grade 3) to treatment a monoclonal antibody/components of the study intervention Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease Is being treated for pericardial effusion, or has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible Has an active infection requiring systemic therapy Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab + Cisplatin + Pemetrexed<br>Pembrolizumab 200 mg IV every 3 weeks (Q3W) in combination with Cisplatin 75 mg/m^2 IV, and Pemetrexed 500 mg/m^2 IV for 4-6 cycles followed by monotherapy of Pembrolizumab up to 35 cycles from the first dose of the study in treatment phase (approximately 2 years). | Drug: Pembrolizumab<br>* Participants will receive Pembrolizumab 200 mg IV every 3 weeks (Q3W) until disease progression, or until participant has received 35 administrations of Pembrolizumab (approximately 2 years).<br>* Other names: MK-3475;Drug: Pemetrexed<br>* Participants will receive Pemetrexed 500 mg/m^2 IV on Day 1 of each cycle up to 4-6 cycles where each cycle = 3 weeks<br>* Other names: Alimta;Drug: Cisplatin<br>* Participants will receive Cisplatin 75 mg/m^2 IV on Day 1 of each cycle up to 4-6 cycles where each cycle = 3 weeks<br>* Other names: Platinol-AQ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events (AEs), Version 5.0 (CTCAE) | DLTs will be assessed during the first cycle (21 days) and are defined as Grade (Gr) 4 hematologic toxicities (any period), except neutropenia and febrile neutropenia. Gr 4 neutropenia lasting >7 days despite appropriate supportive treatment. Gr 4 febrile neutropenia (any period) only if the event is considered as clinically significant for the participant deemed by investigator and sponsor. Any Gr 4 non-hematologic toxicity (except laboratory test abnormal including transient electrolyte abnormalities). Any Gr 3 non-hematologic toxicity lasting >72 hours despite appropriate supportive treatment (not laboratory). Clinical test value abnormality is any Gr 4 laboratory test value abnormality. Any Gr 3 laboratory test value abnormality lasting >7 days. The start of the second course is delayed by more than 2 weeks (more than 35 days after the first dose) due to toxicity related to study procedures or any Gr 5. | Up to 3 weeks | 
| Number of Participants Who Experience an Adverse Event (AE) | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention whether or not considered related to the study intervention. | Up to approximately 33 months | 
| Number of Participants Who Discontinue Study Treatment Due to an AE | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention whether or not considered related to the study intervention. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (RECIST) as Assessed by Investigator | ORR is defined as the percentage of participants who have a Complete Response (CR): Disappearance of all target lesions) or a Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experience a CR or PR based on modified RECIST will be presented | Up to approximately 31 months | 
| Disease Control Rate (DCR) per modified RECIST as Assessed by Investigator | DCR is defined as the percentage of participants who have a Complete Response (CR): Disappearance of all target lesions) or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. | Up to approximately 31 months | 
| Duration of Response (DOR) per modified RECIST as Assessed by Investigator | For participants who demonstrate a confirmed complete response (CR): Disappearance of all target lesions) or confirmed Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions) per RECIST, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. | Up to approximately 31 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)