Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04895722
Recruitment Status : Recruiting
First Posted : May 20, 2021
Last Update Posted : September 24, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: Pembrolizumab Biological: Pembrolizumab/Quavonlimab Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : June 25, 2021
Estimated Primary Completion Date : September 19, 2024
Estimated Study Completion Date : September 19, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Pembrolizumab
Participants receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years.
Biological: Pembrolizumab
400 mg pembrolizumab administered via IV infusion.
Other Names:
  • MK-3475
  • Keytruda®

Experimental: Pembrolizumab/Quavonlimab
Participants receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years.
Biological: Pembrolizumab/Quavonlimab
Co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) fixed-dose combination (FDC) administered via IV infusion.
Other Name: MK-1308A




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT04895722


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 25 study locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04895722    
Other Study ID Numbers: 1308A-008
2020-005114-18 ( EudraCT Number )
MK-1308A-008 ( Other Identifier: Merck )
First Posted: May 20, 2021    Key Record Dates
Last Update Posted: September 24, 2021
Last Verified: September 2021
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
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:
Layout table for MeSH terms
Colorectal Neoplasms
Microsatellite Instability
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Genomic Instability
Pathologic Processes
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents