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Evaluation of Pembrolizumab (MK-3475) or Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008)

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ClinicalTrials.gov Identifier: NCT04895722
Recruitment Status : Recruiting
First Posted : May 20, 2021
Last Update Posted : October 13, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE May 18, 2021
First Posted Date  ICMJE May 20, 2021
Last Update Posted Date October 13, 2021
Actual Study Start Date  ICMJE June 25, 2021
Estimated Primary Completion Date September 19, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2021)
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 39 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) per RECIST 1.1. as assessed by BICR.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2021)
  • Duration of Response (DOR) per RECIST 1.1 as assessed by BICR [ Time Frame: Up to approximately 39 months ]
    DOR is defined as the time from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.
  • Progression-Free Survival (PFS) per RECIST 1.1 as assessed by BICR [ Time Frame: Up to approximately 39 months ]
    PFS is defined as the time from randomization (or first dose) to the first documented PD per RECIST 1.1 assessed by BICR or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.
  • Overall Survival (OS) [ Time Frame: Up to approximately 39 months ]
    OS is defined as the time from randomization (or first dose) to death due to any cause.
  • Number of participants who experienced an Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants with an AE will be reported.
  • Number of participants discontinuing study treatment due to an AE [ Time Frame: Up to approximately 24 months ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants that discontinue study treatment due to an AE will be reported.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Pembrolizumab (MK-3475) or Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008)
Official Title  ICMJE A Phase 2, Multicenter, Multi Arm, Study to Evaluate Pembrolizumab (MK-3475) or MK-1308A (Co-formulated Quavonlimab (MK-1308)/Pembrolizumab) in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer: (MK-1308A-008)
Brief Summary The purpose of this study is to assess the efficacy and safety of pembrolizumab or co-formulated pembrolizumab/quavonlimab in participants with MSI-H or dMMR Metastatic Stage IV Colorectal Cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Biological: Pembrolizumab
    400 mg pembrolizumab administered via IV infusion.
    Other Names:
    • MK-3475
    • Keytruda®
  • Biological: Pembrolizumab/Quavonlimab
    Co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) fixed-dose combination (FDC) administered via IV infusion.
    Other Name: MK-1308A
Study Arms  ICMJE
  • Active Comparator: Pembrolizumab
    Participants receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years.
    Intervention: Biological: Pembrolizumab
  • Experimental: Pembrolizumab/Quavonlimab
    Participants receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years.
    Intervention: Biological: Pembrolizumab/Quavonlimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 18, 2021)
240
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 19, 2024
Estimated Primary Completion Date September 19, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has a histologically confirmed diagnosis of Stage IV CRC adenocarcinoma (as defined by American Joint Committee on Cancer [AJCC] version 8)
  • Has locally confirmed dMMR/MSI-H
  • Has a life expectancy of at least 3 months
  • Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 at screening and within 3 days before Cycle 1 Day 1
  • Female participants are eligible to participate if not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP), or if a WOCBP then is using a contraceptive method that is highly effective or is abstinent on a long-term and persistent basis, during the intervention period and for at least 120 days after the last dose of study intervention
  • Has measurable disease per RECIST 1.1 as assessed by BICR
  • Has adequate organ function

Cohort A:

  • Has been previously treated for their disease and radiographically progressed per RECIST 1.1 on or after or could not tolerate standard treatment, which must include all of the following agents if approved and locally available in the country where the participant is randomized:

    • Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as equivalent to fluorouracil in prior therapy)
    • With or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (e.g., bevacizumab)
    • At least one of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for rat sarcoma viral oncogene homolog (RAS) wild-type participants with left-sided tumors
  • Must not have had prior exposure to PD-1 or PD-L1 therapies as treatment for this disease

Cohort B:

- Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for this disease

Cohort C:

  • Has radiographically progressed on-treatment with an anti-PD-1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other therapies
  • Has had 0 to 1 prior systemic fluoropyrimidine based chemotherapy regimens
  • Must not have been treated in Cohort A

Exclusion Criteria:

  • Has received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor
  • Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
  • Has not recovered adequately from a surgery procedure, and/or has any complications from a prior surgery before starting study intervention
  • Has received prior radiotherapy within 2 weeks of start of study intervention
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before 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 to the first dose of study medication
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab, quavonlimab and/or any of their excipients
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
  • Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy (e.g., tuberculosis, known viral or bacterial infections, etc.)
  • Has a known history of Human Immunodeficiency Virus (HIV) infection
  • Has known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable Hepatitis B Virus [HBV] deoxyribonucleic acid [DNA]) or active Hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected or anti-HCV antibodypositive) infection
  • Is pregnant, or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study intervention
  • Has had an allogenic tissue/solid organ transplant
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE France,   Germany,   Italy,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04895722
Other Study ID Numbers  ICMJE 1308A-008
2020-005114-18 ( EudraCT Number )
MK-1308A-008 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP