A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT05217446
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to learn about the effects of three study medicines (encorafenib, cetuximab, and pembrolizumab) given together for the treatment of colorectal cancer that:
* is metastatic (spread to other parts of the body);
* has the condition of genetic hypermutability (tendency to mutation) or impaired DNA mismatch repair (MMR)
* has a certain type of abnormal gene called "BRAF" and;
* has not received prior treatment.
All participants in this study will receive pembrolizumab at the study clinic as an intravenous (IV) infusion (given directly into a vein) at the study clinic.
In addition, half of the participants will take encorafenib by mouth at home every day and cetuximab by IV infusion at the study clinic.
The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 107
- Locally confirmed microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) stage IV colorectal carcinoma
- Locally confirmed BRAF V600E mutation in tumor tissue or blood
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Have not received prior systemic regimens for metastatic disease.
- Measurable disease per RECIST 1.1
- Adequate organ function
- Colorectal adenocarcinoma that is RAS mutant or for which RAS mutation status is unknown
- Known active central nervous system metastases and/or carcinomatous meningitis; leptomeningeal disease
- Immunodeficiency or active autoimmune disease requiring systemic treatment in the past 2 years
- Presence of acute or chronic pancreatitis
- Clinically significant cardiovascular diseases (eg, thromboembolic or cerebrovascular accident events ≤ 12 wks prior)
- Received a live or live-attenuated vaccine within 30 days of planned start of study medication
- Previous treatment with any selective BRAF inhibitor (eg, encorafenib, dabrafenib, vemurafenib, XL281/BMS-908662) or any epidermal growth factor receptor (EGFR) inhibitor (eg, cetuximab, panitumumab).
- Previous treatment with an immune checkpoint inhibitor (eg, anti-programmed cell death [PD-1], anti-PD-L1 or anti-PD-L2 agent); or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: pembrolizumab Pembrolizumab Participants receive pembrolizumab IV. Arm A: encorafenib, cetuximab and pembrolizumab Cetuximab Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV. Arm A: encorafenib, cetuximab and pembrolizumab Pembrolizumab Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV. Arm A: encorafenib, cetuximab and pembrolizumab Encorafenib Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Duration of study, approximately 45 months PFS per investigator, defined as the time from randomization until PD based on investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first:
- Secondary Outcome Measures
Name Time Method Incidence of adverse events Duration of study, approximately 45 months Incidence and severity of AEs graded according to the NCI CTCAE v4.03: encorafenib and cetuximab + pembrolizumab (Arm A) vs pembrolizumab (Arm B)
Overall Survival (OS) Duration of study, approximately 45 months OS is defined as the time from the date of randomization to the date of death due to any cause: encorafenib and cetuximab + pembrolizumab (Arm A) vs pembrolizumab (Arm B)
Objective Response (OR) Duration of study, approximately 45 months OR is defined as a CR or PR per RECIST version 1.1 recorded from the date of randomization until date of first documentation of PD, death, or start of new anti-cancer therapy: encorafenib and cetuximab + pembrolizumab (Arm A) vs pembrolizumab (Arm B)
Trial Locations
- Locations (64)
Saskatoon Cancer Center
🇨🇦Saskatoon, Saskatchewan, Canada
Przychodnia Lekarska KOMED
🇵🇱Konin, Wielkopolskie, Poland
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza
🇵🇱Brzozow, Poland
Narodny onkologicky ustav
🇸🇰Bratislava, Slovakia
Mayo Clinic Building - Phoenix
🇺🇸Phoenix, Arizona, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
Keck School of Medicine of USC
🇺🇸Los Angeles, California, United States
LAC USC Medical Center
🇺🇸Los Angeles, California, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
USC/Norris Comprehensive Cancer Center / Investigational Drug Services
🇺🇸Los Angeles, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Keck Hospital of USC Pasadena
🇺🇸Pasadena, California, United States
Mount Sinai Cancer Center
🇺🇸Miami Beach, Florida, United States
The West Clinic, PLLC dba West Cancer Center
🇺🇸Germantown, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Imelda General Hospital
🇧🇪Bonheiden, Antwerpen, Belgium
Institut Jules Bordet
🇧🇪Anderlecht, Bruxelles-capitale, Région DE, Belgium
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Bruxelles-capitale, Région DE, Belgium
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Sunnybrook Health Sciences - Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Hradec Králové, Czechia
Fakultni Thomayerova nemocnice
🇨🇿Prague, Praha 4, Czechia
Fakultni nemocnice Bulovka
🇨🇿Prague, Praha 8, Czechia
Rigshospitalet
🇩🇰Copenhagen, Hovedstaden, Denmark
Herlev and Gentofte Hospital
🇩🇰Copenhagen, Hovedstaden, Denmark
Aalborg Universitetshospital, Syd
🇩🇰Aalborg, Nordjylland, Denmark
Vejle Sygehus
🇩🇰Vejle, Syddanmark, Denmark
Hôpital Européen Georges Pompidou
🇫🇷Paris Cedex 15, Paris, France
CHU Estaing
🇫🇷Clermont Ferrand, France
Centre Hospitalier Universitaire Estaing
🇫🇷Clermont-Ferrand, France
Institut Regional du Cancer de Montpellier - ICM Val d'Aurelle
🇫🇷Montpellier Cedex 5, France
Hôpital Saint Antoine
🇫🇷Paris, France
Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
🇩🇪Muenchen, Bayern, Germany
Facharztzentrum Eppendorf
🇩🇪Hamburg, Germany
Policlinico Universitario Monserrato
🇮🇹Monserrato, Cagliari, Italy
Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" Piazza Luigi Miraglia, 2 Napoli
🇮🇹Napoli, Campania, Italy
Ospedale di Guastalla
🇮🇹Guastalla, Emilia-romagna, Italy
IRCCS Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milan, Milano, Italy
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
🇮🇹Candiolo, Torino, Italy
Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno
🇮🇹Livorno, Toscana, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Veneto, Italy
Fondazione Poliambulanza Istituto Ospedaliero
🇮🇹Brescia, Italy
Istituto Europeo di Oncologia IRCCS
🇮🇹Milano, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Maastricht UMC+
🇳🇱Maastricht, Limburg, Netherlands
Oslo Universitetssykehus Ullevål
🇳🇴Oslo, Norway
CHUS - Hospital Clinico Universitario
🇪🇸Santiago de Compostela, A Coruña [LA Coruña], Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [barcelona], Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Catalunya [cataluña], Spain
Institut Català d'Oncologia - L'Hospitalet
🇪🇸L'Hospitalet de Llobregat, Catalunya [cataluña], Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Madrid, Comunidad DE, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Aberdeen Royal Infirmary
🇬🇧Aberdeen, Aberdeen CITY, United Kingdom
Heartlands Hospital
🇬🇧Birmingham, United Kingdom