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

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04895722
Collaborator
(none)
320
55
5
50.2
5.8
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of co-formulated pembrolizumab/quavonlimab versus other treatments in participants with MSI-H or dMMR Metastatic Stage IV Colorectal Cancer.

Condition or Disease Intervention/Treatment Phase
  • Biological: Pembrolizumab
  • Biological: Pembrolizumab/Quavonlimab
  • Biological: Pembrolizumab/Favezelimab
  • Biological: Pembrolizumab/Vibostolimab
  • Biological: MK-4830
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
320 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 MK-1308A (Co-formulated Quavonlimab (MK-1308)/Pembrolizumab) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer: (MK-1308A-008)
Actual Study Start Date :
Jun 25, 2021
Anticipated Primary Completion Date :
Sep 19, 2024
Anticipated Study Completion Date :
Aug 30, 2025

Arms and Interventions

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 or 200 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 Names:
  • MK-1308A
  • Experimental: Pembrolizumab/Favezelimab

    Participants receive co-formulated pembrolizumab/favezelimab (200 mg/800 mg) every 3 weeks (Q3W) for up to approximately 2 years.

    Biological: Pembrolizumab/Favezelimab
    Co-formulated pembrolizumab/favezelimab (200 mg/800 mg) FDC administered via IV infusion
    Other Names:
  • MK-4280A
  • Experimental: Pembrolizumab/Vibostolimab

    Participants receive co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years.

    Biological: Pembrolizumab/Vibostolimab
    Co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) FDC administered via IV infusion
    Other Names:
  • MK-7684A
  • Experimental: Pembrolizumab Plus MK-4830

    Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.

    Biological: Pembrolizumab
    400 mg or 200 mg pembrolizumab administered via IV infusion.
    Other Names:
  • MK-3475
  • Keytruda®
  • Biological: MK-4830
    800 mg MK-4830 administered via IV infusion

    Outcome Measures

    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) [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. ORR as assessed by BICR will be presented.

    Secondary Outcome Measures

    1. Duration of Response (DOR) per RECIST 1.1 as assessed by BICR [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. DOR as assessed by BICR will be presented.

    2. Progression-Free Survival (PFS) per RECIST 1.1 as assessed by BICR [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 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. PFS as assessed by BICR will be presented.

    3. PFS per RECIST 1.1 as assessed by Investigator [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 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. PFS as assessed by investigator will be presented.

    4. ORR per RECIST 1.1 as assessed by Investigator [Up to approximately 39 months]

      ORR is defined as the percentage of participants who have 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. ORR as assessed by investigator will be presented.

    5. DOR per RECIST 1.1 as assessed by Investigator [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 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. DOR as assessed by investigator will be presented.

    6. Overall Survival (OS) [Up to approximately 39 months]

      OS is defined as the time from randomization (or first dose) to death due to any cause. OS will be presented.

    7. Number of Participants Who Experienced an Adverse Event (AE) [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 presented.

    8. Number of Participants Discontinuing Study Treatment Due to an AE [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 presented.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • Female participants are eligible to participate if not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP), or if a WOCBP then uses 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 the site and verified by BICR

    • Submit an archival or newly obtained tumor tissue sample that has not been previously irradiated; formalin-fixed, paraffin embedded (FFPE) blocks are preferred to slides.

    • 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. Prior EGFR therapy is optional for patients with right sided RAS Wild-type (WT) tumors.

    Cohort B:
    • Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for this disease
    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, favezelimab, vibostolimab, MK-4830, 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 a history of acute or chronic pancreatitis

    • Has neuromuscular disorders associated with an elevated creatine kinase

    • Has urine protein ≥1 gram/24 hours

    • 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 antibody positive) infection

    • Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study intervention administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.

    • Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before randomization/allocation

    • 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

    • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

    • Has had an allogenic tissue/solid organ transplant

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mid Florida Cancer Center ( Site 1519) Orange City Florida United States 32763
    2 University Cancer & Blood Center, LLC ( Site 1521) Athens Georgia United States 30607
    3 University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P Chicago Illinois United States 60637
    4 UPMC Hillman Cancer Center ( Site 1516) Pittsburgh Pennsylvania United States 15232
    5 Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1509) Nashville Tennessee United States 37232
    6 Baylor Scott & White Medical Center - Temple-Division of Hematology/Oncology ( Site 1549) Temple Texas United States 76508
    7 Northwest Medical Specialties, PLLC ( Site 1546) Tacoma Washington United States 98405
    8 UZ Brussel ( Site 0105) Brussels Bruxelles-Capitale, Region De Belgium 1090
    9 Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 0102) Yvoir Namur Belgium 5530
    10 UZ Leuven ( Site 0101) Leuven Vlaams-Brabant Belgium 3000
    11 The Moncton Hospital-Oncology ( Site 0307) Moncton New Brunswick Canada E1C 6Z8
    12 McGill University Health Centre-CIM - Oncology ( Site 0306) Montréal Quebec Canada H4A 3J1
    13 Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service d'Hepato-Gastro-Enterologie et Marseille Bouches-du-Rhone France 13385
    14 Centre Georges François Leclerc ( Site 0506) Dijon Cote-d Or France 21079
    15 CHU Rangueil-Digestive oncology department ( Site 0502) Toulouse Haute-Garonne France 31059
    16 Hopital Claude Huriez - CHU de Lille ( Site 0510) Lille Nord France 59037
    17 Centre Hospitalier Universitaire de Poitiers ( Site 0511) Poitiers Vienne France 86021
    18 Hôpital Saint Antoine-Oncologie médicale ( Site 0508) Paris France 75571
    19 Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0601) Dresden Sachsen Germany 01307
    20 Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0604) Berlin Germany 10117
    21 Asklepios Altona-Oncology ( Site 0602) Hamburg Germany 22763
    22 Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0802) Milan Lombardia Italy 20133
    23 Istituto Oncologico Veneto IRCCS ( Site 0804) Padova Veneto Italy 35128
    24 Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0803) Napoli Italy 80131
    25 Kyungpook National University Chilgok Hospital-Hematology/oncology ( Site 1103) Daegu Taegu-Kwangyokshi Korea, Republic of 41404
    26 Korea University Anam Hospital ( Site 1107) Seoul Korea, Republic of 02841
    27 Seoul National University Hospital-Internal Medicine ( Site 1101) Seoul Korea, Republic of 03080
    28 Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1104) Seoul Korea, Republic of 03722
    29 Asan Medical Center-Department of Oncology ( Site 1105) Seoul Korea, Republic of 05505
    30 Samsung Medical Center-Division of Hematology/Oncology ( Site 1102) Seoul Korea, Republic of 06351
    31 The Catholic Univ. of Korea Seoul St. Mary's Hospital-Medical Oncology ( Site 1106) Seoul Korea, Republic of 06591
    32 Powiatowe Centrum Zdrowia ( Site 0911) Brzeziny Lodzkie Poland 95-060
    33 Luxmed Onkologia sp. z o. o. ( Site 0915) Warszawa Mazowieckie Poland 01-748
    34 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site Warszawa Mazowieckie Poland 02-034
    35 Mrukmed-Mrukmed ( Site 0901) Rzeszow Podkarpackie Poland 35-021
    36 Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0903) Koszalin Zachodniopomorskie Poland 75-581
    37 Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1001) Saint Petersburg Leningradskaya Oblast Russian Federation 198255
    38 Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology-Clinical Pharmacology and Chemotherapy Moscow Moskva Russian Federation 115478
    39 First Moscow State Medical University I.M. Sechenov-Interhospital Institution Health Management Cl Moscow Moskva Russian Federation 119991
    40 Rostov Cancer Research Institute ( Site 1014) Rostov on Don Rostovskaya Oblast Russian Federation 344037
    41 GBUZ SPb CRPCstmc(o) ( Site 1005) Sankt- Peterburg Sankt-Peterburg Russian Federation 197758
    42 Republican Clinical Oncology Dispensary-Chemotherapy #3 ( Site 1006) Kazan Tatarstan, Respublika Russian Federation 420029
    43 Hospital Universitario Central de Asturias-Medical Oncology ( Site 1203) Oviedo Asturias Spain 33011
    44 Hospital Universitario Marqués de Valdecilla ( Site 1202) Santander Cantabria Spain 39008
    45 Hospital Universitari Vall d'Hebron ( Site 1201) Barcelona Spain 08035
    46 HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1206) Madrid Spain 28007
    47 Hospital Clinico San Carlos-Oncology Department ( Site 1204) Madrid Spain 28040
    48 Baskent University Dr. Turgut Noyan Research and Training Center ( Site 1303) Adana Turkey 01250
    49 Hacettepe Universitesi-oncology hospital ( Site 1301) Ankara Turkey 06230
    50 Ankara City Hospital-Medical Oncology ( Site 1306) Ankara Turkey 06800
    51 TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1305) Istanbul Turkey 34722
    52 Beatson West of Scotland Cancer Centre-Clinical Trials Unit ( Site 1401) Glasgow Glasgow City United Kingdom G15 6HG
    53 UCLH-Cancer Clinical Trials Unit ( Site 1402) London London, City Of United Kingdom NW1 2PG
    54 Velindre Cancer Centre-Research and Development ( Site 1415) Cardiff United Kingdom CF14 2TL
    55 University Hospital Coventry & Warwickshire ( Site 1406) Coventry United Kingdom CV2 2DX

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT04895722
    Other Study ID Numbers:
    • 1308A-008
    • MK-1308A-008
    • 2020-005114-18
    First Posted:
    May 20, 2021
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Sharp & Dohme LLC
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 18, 2022