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).
Overview
- Phase
- Phase 1
- Intervention
- Cisplatin
- Conditions
- Mesothelioma
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 19
- Locations
- 4
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 9 months ago
Overview
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.
Investigators
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
Arms & Interventions
Pembrolizumab + Cisplatin + Pemetrexed
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).
Intervention: Cisplatin
Pembrolizumab + Cisplatin + Pemetrexed
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).
Intervention: Pembrolizumab
Pembrolizumab + Cisplatin + Pemetrexed
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).
Intervention: Pemetrexed
Outcomes
Primary Outcomes
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)
Time Frame: Up to 3 weeks (through Cycle 1 [21 days])
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.
Number of Participants With One or More Adverse Events (AEs)
Time Frame: Up to approximately 34 months
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.
Number of Participants Discontinuing Study Treatment Due to an AE
Time Frame: Up to approximately 2 years
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.
Secondary Outcomes
- 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)