Clinical Trials /

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

NCT04153565

Description:

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

Related Conditions:
  • Malignant Pleural Mesothelioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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).

Clinical Trial IDs

  • ORG STUDY ID: 3475-A17
  • SECONDARY ID: MK-3475-A17
  • SECONDARY ID: 195054
  • NCT ID: NCT04153565

Conditions

  • Mesothelioma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, MK-3475PBZ @ 200 mg/m2 IV + CIS @ 75 mg/m2 IV + PMX @ 500 mg/m2 IV
PemetrexedAlimtaPBZ @ 200 mg/m2 IV + CIS @ 75 mg/m2 IV + PMX @ 500 mg/m2 IV
CisplatinPlatinol-AQPBZ @ 200 mg/m2 IV + CIS @ 75 mg/m2 IV + PMX @ 500 mg/m2 IV

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
PBZ @ 200 mg/m2 IV + CIS @ 75 mg/m2 IV + PMX @ 500 mg/m2 IVExperimentalPBZ @ 200 mg/m2 IV every 3 weeks (Q3W) in combination with CIS @ 75 mg/m2 IV, and PMX @ 500 mg/m2 IV for 4-6 cycles followed by monotherapy of PBZ up to 35 cycles from the first dose of the study in treatment phase (approximately 2 years)
  • Pembrolizumab
  • Pemetrexed
  • Cisplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Has histologically confirmed diagnosis of advanced/unresectable MPM.

          -  Have at least one measurable disease, which is treatment naïve, assessed by the local
             site investigator per modified RECIST

          -  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-PD-1, anti-PD-L1, or 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 for MPM.

             o 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 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.

             o 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.

             o 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 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 that required steroids or has current
             pneumonitis.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Who Experience a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events (AEs), Version 5.0 (CTCAE)
Time Frame:Up to 3 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (RECIST) as Assessed by Investigator
Time Frame:Up to approximately 31 months
Safety Issue:
Description: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
Measure:Disease Control Rate (DCR) per modified RECIST as Assessed by Investigator
Time Frame:Up to approximately 31 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) per modified RECIST as Assessed by Investigator
Time Frame:Up to approximately 31 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)

Last Updated

January 3, 2020