A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer

NCT ID: NCT05217446

Last Updated: 2026-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-11

Study Completion Date

2027-01-26

Brief Summary

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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

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Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is an open-label, multicenter study of encorafenib and cetuximab plus pembrolizumab (Triplet Arm \[Arm A\]) versus pembrolizumab alone (Control Arm \[Arm B\]) as first-line treatment in participants with BRAF inhibitor (BRAF) V600E-mutant and microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) mCRC. Randomization will be stratified by ECOG (0 vs 1)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: encorafenib, cetuximab and pembrolizumab

Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.

Group Type EXPERIMENTAL

Encorafenib

Intervention Type DRUG

capsule

Cetuximab

Intervention Type BIOLOGICAL

IV

Pembrolizumab

Intervention Type BIOLOGICAL

IV

Arm B: pembrolizumab

Participants receive pembrolizumab IV.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type BIOLOGICAL

IV

Interventions

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Encorafenib

capsule

Intervention Type DRUG

Cetuximab

IV

Intervention Type BIOLOGICAL

Pembrolizumab

IV

Intervention Type BIOLOGICAL

Other Intervention Names

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PF-07263896 LGX818 ONO-7702 W0090 Erbitux Keytruda®, MK-3475

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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).
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Mayo Clinic Building - Phoenix

Phoenix, Arizona, United States

Site Status

Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

Mount Sinai Cancer Center

Miami Beach, Florida, United States

Site Status

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Imelda General Hospital

Bonheiden, Antwerpen, Belgium

Site Status

Institut Jules Bordet

Anderlecht, Bruxelles-capitale, Région de, Belgium

Site Status

Cliniques universitaires Saint-Luc

Brussels, Bruxelles-capitale, Région de, Belgium

Site Status

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Site Status

Sunnybrook Health Sciences - Odette Cancer Centre

Toronto, Ontario, Canada

Site Status

Saskatoon Cancer Center

Saskatoon, Saskatchewan, Canada

Site Status

Fakultni nemocnice Hradec Kralove

Hradec Králové, Hradec Králové, Czechia

Site Status

Fakultni Thomayerova nemocnice

Prague, Praha 4, Czechia

Site Status

Fakultni nemocnice Bulovka

Prague, Praha 8, Czechia

Site Status

Rigshospitalet

Copenhagen, Capital Region, Denmark

Site Status

Herlev and Gentofte Hospital

Copenhagen, Capital Region, Denmark

Site Status

Aalborg Universitetshospital, Syd

Aalborg, North Denmark, Denmark

Site Status

Vejle Sygehus

Vejle, Region Syddanmark, Denmark

Site Status

Hôpital Européen Georges Pompidou

Paris, Paris, France

Site Status

Centre Hospitalier Universitaire Estaing

Clermont-Ferrand, , France

Site Status

CHU Estaing

Clermont-Ferrand, , France

Site Status

Institut Regional du Cancer de Montpellier - ICM Val d'Aurelle

Montpellier, , France

Site Status

Hôpital Saint Antoine

Paris, , France

Site Status

Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie

Munich, Bavaria, Germany

Site Status

Facharztzentrum Eppendorf

Hamburg, , Germany

Site Status

Policlinico Universitario Monserrato

Monserrato, Cagliari, Italy

Site Status

Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" Piazza Luigi Miraglia, 2 Napoli

Napoli, Campania, Italy

Site Status

Ospedale di Guastalla

Guastalla, Emilia-Romagna, Italy

Site Status

IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Site Status

ASST Grande Ospedale Metropolitano Niguarda

Milan, Milano, Italy

Site Status

Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, Italy

Site Status

Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno

Livorno, Tuscany, Italy

Site Status

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, Italy

Site Status

Istituto Oncologico Veneto IRCCS

Padua, Veneto, Italy

Site Status

Fondazione Poliambulanza Istituto Ospedaliero

Brescia, , Italy

Site Status

Istituto Europeo di Oncologia IRCCS

Milan, , Italy

Site Status

Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Site Status

Maastricht UMC+

Maastricht, Limburg, Netherlands

Site Status

Oslo Universitetssykehus Ullevål

Oslo, , Norway

Site Status

Przychodnia Lekarska KOMED

Konin, Greater Poland Voivodeship, Poland

Site Status

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza

Brzozów, , Poland

Site Status

Narodny onkologicky ustav

Bratislava, , Slovakia

Site Status

CHUS - Hospital Clinico Universitario

Santiago de Compostela, A Coruña [LA Coruña], Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona], Spain

Site Status

Hospital Clínic de Barcelona

Barcelona, Catalunya [cataluña], Spain

Site Status

Institut Català d'Oncologia - L'Hospitalet

L'Hospitalet de Llobregat, Catalunya [cataluña], Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Comunidad de, Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Site Status

Hospital General Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Aberdeen Royal Infirmary

Aberdeen, Aberdeen CITY, United Kingdom

Site Status

Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada Czechia Denmark France Germany Italy Netherlands Norway Poland Slovakia Spain United Kingdom

References

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Elez E, Kopetz S, Tabernero J, Bekaii-Saab T, Taieb J, Yoshino T, Manji G, Fernandez K, Abbattista A, Zhang X, Morris VK. SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAFV600E-mutant mCRC. Future Oncol. 2024 Apr;20(11):653-663. doi: 10.2217/fon-2022-1249. Epub 2023 Oct 10.

Reference Type DERIVED
PMID: 37815847 (View on PubMed)

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C4221022

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Other Identifiers

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SEAMARK

Identifier Type: OTHER

Identifier Source: secondary_id

2024-512119-34-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

KEYNOTE-D31

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3475-D31

Identifier Type: OTHER

Identifier Source: secondary_id

C4221022

Identifier Type: -

Identifier Source: org_study_id

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