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

NCT04153565 | Completed Phase 1 Results

• 3 other identifiers: 3475-A17MK-3475-A17195054
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Mesothelioma

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 1, Per Common Terminology Criteria for Adverse Events (AEs), Version 5.0 (CTCAE)

  DLTs were assessed during Cycle 1 (21 days) and defined as any of the following, if considered by investigator to be related to any of the study interventions: Grade 4 hematologic toxicities, except neutropenia and febrile neutropenia; Grade 4 neutropenia lasting \>7 days despite appropriate supportive treatment; Grade 4 febrile neutropenia only if the event considered as clinically significant by investigator and sponsor; any Grade 4 non-hematologic toxicity (except laboratory test abnormal including transient electrolyte abnormalities); any Grade 3 non-hematologic toxicity lasting \>72 hours despite appropriate supportive treatment (not laboratory); and any Grade 4 laboratory test value abnormality; any Grade 3 laboratory test value abnormality lasting \>7 days; delay in start of second course of more than 2 weeks (more than 35 days after the first dose) due to toxicity related to study procedures; any Grade 5 toxicity.

  Up to 3 weeks (through Cycle 1 [21 days])

• Number of Participants With One or More Adverse Events (AEs)

  An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE.

  Up to approximately 34 months

• Number of Participants Discontinuing Study Treatment Due to an AE

  An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE.

  Up to approximately 2 years

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to approximately 31 months

• Disease Control Rate (DCR)

  Up to approximately 31 months

• Duration of Response (DOR)

  Up to approximately 31 months

Study Arms (1)

Pembrolizumab + Cisplatin + Pemetrexed

EXPERIMENTAL

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; Drug: Pemetrexed; Drug: Cisplatin

Interventions

Pembrolizumab DRUG

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).

Also known as: Keytruda, MK-3475

Pembrolizumab + Cisplatin + Pemetrexed

Pemetrexed DRUG

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

Also known as: Alimta

Pembrolizumab + Cisplatin + Pemetrexed

Cisplatin DRUG

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

Also known as: Platinol-AQ

Pembrolizumab + Cisplatin + Pemetrexed

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (4)

Hyogo College of Medicine Hospital ( Site 0003)

Nishinomiya, Hyōgo, 663-8501, Japan

Location

Kanagawa Cancer Center ( Site 0004)

Yokohama, Kanagawa, 241-8515, Japan

Location

JOHAS Okayama Rosai Hospital ( Site 0002)

Okayama, 702-8055, Japan

Location

National Cancer Center Hospital ( Site 0001)

Tokyo, 104-0045, Japan

Location

Related Publications (1)

• Kijima T, Kato T, Goto Y, Kuribayashi K, Mikami K, Negi Y, Murakami S, Yoshida T, Homma M, Wakana A, Noguchi K, Fujimoto N. KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin-Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma. Cancer Sci. 2025 Aug;116(8):2208-2217. doi: 10.1111/cas.70082. Epub 2025 May 23.

  PMID: 40407381 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Mesothelioma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp& Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 6, 2019
• Study Start: December 9, 2019
• Primary Completion: September 21, 2022
• Study Completion: September 21, 2022
• Last Updated: July 17, 2025
• Results First Posted: March 22, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

JP (4)