Clinical trial NCT04153565: A Study of Pembrolizumab in Combination With Cisplatin and Pemetrexed in Advanced Malignant Pleural Mesothelioma (MPM) (MK-3475-A17)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-11-06
Enrollment: 19
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Up to 3 weeks (through Cycle 1 [21 days])
measure: Number of Participants With One or More Adverse Events (AEs)
timeFrame: Up to approximately 34 months
measure: Number of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 31 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 31 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 31 months
Other outcomes:
Locations:
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine Hospital ( Site 0003)
state: Hyogo
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center ( Site 0004)
state: Kanagawa
city: Okayama
country: Japan
facility: JOHAS Okayama Rosai Hospital ( Site 0002)
city: Tokyo
country: Japan
facility: National Cancer Center Hospital ( Site 0001)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: