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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Mesothelioma

Treatments: Drug: Pembrolizumab; Drug: Cisplatin; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT04153565

MK-3475-A17 (Other Identifier)

195054 (Registry Identifier)

3475-A17

Details and patient eligibility

About

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.

Enrollment: 19 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Pembrolizumab + Cisplatin + Pemetrexed

Experimental group

Description:

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).

Treatment:

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: Cisplatin