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).
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
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)
- 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 46 months
ORR was 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 is presented.
Trial sites (109)
| Facility | City | Region | Status |
| 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.
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