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Clinical Trials in the UK / NCT04895722
Active, not recruiting Phase 2

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/KEYSTEP-008).

NCT04895722 · tracked via the Priya Life Science UK tracker
Sponsor
Merck Sharp & Dohme LLC
Phase
Phase 2
Started
2021-06-25
Last updated
2026-07-02

Condition(s) studied

Colorectal Cancer

Investigational drug(s) / intervention(s)

PembrolizumabPembrolizumab/QuavonlimabPembrolizumab/FavezelimabPembrolizumab/VibostolimabMK-4830

Pembrolizumab: 400 mg or 200 mg pembrolizumab administered via IV infusion.

Pembrolizumab/Quavonlimab: Co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) fixed-dose combination (FDC) administered via IV infusion.

Pembrolizumab/Favezelimab: Co-formulated pembrolizumab/favezelimab (200 mg/800 mg) FDC administered via IV infusion

Pembrolizumab/Vibostolimab: Co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) FDC administered via IV infusion

MK-4830: 800 mg MK-4830 administered via IV infusion

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
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 (within 5 years of Screening) 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 Stage IV dMMR/MSI-H CRC and radiographically progressed 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 * Concurrent active Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] positive and/or detectable Hepatitis B Virus \[HBV\] deoxyribonucleic acid \[DNA\]) and Hepatitis C virus (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid \[RNA\] 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

Primary outcome measure(s)

Trial sites (109)

FacilityCityRegionStatus
Mid Florida Cancer Center ( Site 1519) Orange City Florida
University Cancer & Blood Center, LLC ( Site 1521) Athens Georgia
University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P Chicago Illinois
Icahn School of Medicine at Mount Sinai ( Site 1528) New York New York
Hematology Oncology Associates of Rockland ( Site 1525) Nyack New York
UPMC Hillman Cancer Center ( Site 1516) Pittsburgh Pennsylvania
The West Clinic, PLLC dba West Cancer Center ( Site 1576) Germantown Tennessee
Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1509) Nashville Tennessee
UT Southwestern Medical Center ( Site 1551) Dallas Texas
Baylor Scott & White Medical Center - Temple-Division of Hematology/Oncology ( Site 1549) Temple Texas
Northwest Medical Specialties, PLLC ( Site 1546) Tacoma Washington
UZ Brussel ( Site 0105) Brussels Bruxelles-Capitale, Region de
Cliniques universitaires Saint-Luc-Medical Oncology ( Site 0104) Brussels Bruxelles-Capitale, Region de
Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 0102) Yvoir Namur
UZ Leuven ( Site 0101) Leuven Vlaams-Brabant
AZ Delta vzw ( Site 0106) Roeselare West-Vlaanderen
The Moncton Hospital-Oncology ( Site 0307) Moncton New Brunswick
Sunnybrook Research Institute - Odette Cancer Centre ( Site 0316) Toronto Ontario
McGill University Health Centre-CIM - Oncology ( Site 0306) Montreal Quebec
Instituto de Cancerología ( Site 1610) Medellín Antioquia
Fundación Colombiana de Cancerología Clínica Vida ( Site 1606) Medellín Antioquia
Clinica de la Costa S.A.S. ( Site 1608) Barranquilla Atlántico
Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 1611) Bogotá Bogota D.C.
Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1601) Valledupar Cesar Department
Oncomédica S.A.S ( Site 1602) Montería Departamento de Córdoba
Mediservis del Tolima IPS S.A.S ( Site 1609) Ibague Tolima Department
CIMCA-Hemato-Oncology ( Site 2101) San José Provincia de San José
Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 2102) Santa Ana Provincia de San José
Rigshospitalet ( Site 1904) Copenhagen Capital Region
Regionshospitalet Gødstrup ( Site 1901) Herning Central Jutland
Aalborg Universitetshospital, Syd ( Site 1903) Aalborg North Denmark
Odense Universitetshospital ( Site 1902) Odense Region Syddanmark
North Estonia Medical Centre Foundation-Chemotherapy ( Site 2301) Tallinn Harju
Tartu University Hospital ( Site 2302) Tartu Tartu
Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service d'Hepato-Gastro-Enterologie et Marseille Bouches-du-Rhone
Centre Georges François Leclerc ( Site 0506) Dijon Cote-d Or
CHU Rangueil-Digestive oncology department ( Site 0502) Toulouse Haute-Garonne
Hopital Claude Huriez - CHU de Lille ( Site 0510) Lille Nord
Centre Hospitalier Universitaire de Poitiers ( Site 0511) Poitiers Vienne
Hôpital Saint Antoine-Oncologie médicale ( Site 0508) Paris France

+ 69 more sites — see the full list on the official registry below.

On this site

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04895722 on ClinicalTrials.gov ↗ ← All trials in the UK