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

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ClinicalTrials.gov Identifier: NCT04153565
Recruitment Status : Active, not recruiting
First Posted : November 6, 2019
Last Update Posted : June 29, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Mesothelioma Drug: Pembrolizumab Drug: Pemetrexed Drug: Cisplatin Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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).
Actual Study Start Date : December 9, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 1, 2022


Arm Intervention/treatment
Experimental: PBZ @ 200 mg/m2 IV + CIS @ 75 mg/m2 IV + PMX @ 500 mg/m2 IV
PBZ @ 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)
Drug: Pembrolizumab
Participants will receive PBZ at 200 mg/m2 IV every 3 weeks (Q3W) until disease progression, or until participant has received 35 administrations of PBZ (approximately 2 years)
Other Names:
  • Keytruda
  • MK-3475

Drug: Pemetrexed
Participants will receive PMX @ 500 mg/m2 IV on Day 1 of each cycle up to 4-6 cycles where each cycle = 3 weeks
Other Name: Alimta

Drug: Cisplatin
Participants will receive CIS @ 75 mg/m2 IV on Day 1 of each cycle up to 4-6 cycles where each cycle = 3 weeks
Other Name: Platinol-AQ




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Number of Participants with One or More AEs [ Time Frame: Up to approximately 34 months (up to 90 days after last dose of study treatment) ]
    An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention whether or not considered related to the study intervention

  3. Number of Participants Discontinuing Study Intervention Due to an AE [ Time Frame: Up to approximately 2 years ]
    Tolerability is defined by the degree to which overt AEs of a drug can be tolerated by a participant without discontinuing from the study


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (RECIST) as Assessed by Investigator [ Time Frame: Up to approximately 31 months ]
    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

  2. Disease Control Rate (DCR) per modified RECIST as Assessed by Investigator [ Time Frame: Up to approximately 31 months ]
    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.

  3. Duration of Response (DOR) per modified RECIST as Assessed by Investigator [ Time Frame: Up to approximately 31 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04153565


Locations
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Japan
Hyogo College of Medicine Hospital ( Site 0003)
Nishinomiya, Hyogo, Japan, 663-8501
Kanagawa Cancer Center ( Site 0004)
Yokohama, Kanagawa, Japan, 241-8515
JOHAS Okayama Rosai Hospital ( Site 0002)
Okayama, Japan, 702-8055
National Cancer Center Hospital ( Site 0001)
Tokyo, Japan, 104-0045
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck, Sharpe & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04153565    
Other Study ID Numbers: 3475-A17
MK-3475-A17 ( Other Identifier: Merck Protocol Number )
195054 ( Registry Identifier: JAPIC-CTI )
First Posted: November 6, 2019    Key Record Dates
Last Update Posted: June 29, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Additional relevant MeSH terms:
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Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Cisplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors