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

April 6, 2026 updated by: Pfizer

A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF ENCORAFENIB AND CETUXIMAB PLUS PEMBROLIZUMAB VERSUS PEMBROLIZUMAB ALONE IN PARTICIPANTS WITH PREVIOUSLY UNTREATED BRAF V600E-MUTANT, MSI H/DMMR METASTATIC COLORECTAL CANCER

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

107

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre
      • Parkville, Victoria, Australia, 3052
        • Royal Melbourne Hospital
  • Belgium
    • Antwerpen
      • Bonheiden, Antwerpen, Belgium, 2820
        • Imelda General Hospital
    • Bruxelles-capitale, Région de
      • Anderlecht, Bruxelles-capitale, Région de, Belgium, 1070
        • Institut Jules Bordet
      • Brussels, Bruxelles-capitale, Région de, Belgium, 1200
        • Cliniques Universitaires Saint-luc
  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital - General Campus
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences - Odette Cancer Centre
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N4H4
        • Saskatoon Cancer Center
      • Saskatoon, Saskatchewan, Canada, S7K 0M7
        • Saskatchewan Health Authority
  • Czechia
    • Hradec Králové
      • Hradec Králové, Hradec Králové, Czechia, 500 05
        • Fakultni nemocnice Hradec Kralove
    • Praha 4
      • Prague, Praha 4, Czechia, 14059
        • Fakultni Thomayerova nemocnice
    • Praha 8
      • Prague, Praha 8, Czechia, 180 81
        • Fakultni nemocnice Bulovka
  • Denmark
    • Capital Region
      • Copenhagen, Capital Region, Denmark, 2100
        • Rigshospitalet
      • Copenhagen, Capital Region, Denmark, 2730
        • Herlev and Gentofte Hospital
    • North Denmark
      • Aalborg, North Denmark, Denmark, 9000
        • Aalborg Universitetshospital, Syd
    • Region Syddanmark
      • Vejle, Region Syddanmark, Denmark, 7100
        • Vejle Sygehus
      • Vejle, Region Syddanmark, Denmark, 7100
        • Vejle Hospital, Department of Oncology
  • France
      • Clermont-Ferrand, France, 63100
        • CHU Estaing
      • Clermont-Ferrand, France, 63100
        • Centre Hospitalier Universitaire Estaing
      • Montpellier, France, 34298
        • Institut régional du Cancer de Montpellier - ICM Val d'Aurelle
      • Paris, France, 75571
        • Hopital Saint Antoine
    • Paris
      • Paris, Paris, France, 75015
        • Hôpital Européen Georges Pompidou
  • Germany
      • Hamburg, Germany, 20249
        • Facharztzentrum Eppendorf
    • Bavaria
      • Munich, Bavaria, Germany, 81737
        • Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
  • Italy
      • Brescia, Italy, 25124
        • Fondazione Poliambulanza Istituto Ospedaliero
      • Milan, Italy, 20141
        • Istituto Europeo di Oncologia IRCCS
      • Reggio Emilia, Italy, 42123
        • Arcispedale Santa Maria Nuova
    • Cagliari
      • Monserrato, Cagliari, Italy, 09042
        • Policlinico Universitario Monserrato
    • Campania
      • Naples, Campania, Italy, 80131
        • Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" Piazza Luigi Miraglia, 2 Napoli
    • Emilia-Romagna
      • Guastalla, Emilia-Romagna, Italy, 42016
        • Ospedale di Guastalla
    • Foggia
      • San Giovanni Rotondo, Foggia, Italy, 71013
        • IRCCS Casa Sollievo della Sofferenza
    • Milano
      • Milan, Milano, Italy, 20162
        • ASST Grande Ospedale Metropolitano Niguarda
    • Torino
      • Candiolo, Torino, Italy, 10060
        • Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
    • Tuscany
      • Livorno, Tuscany, Italy, 57124
        • Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno
      • Pisa, Tuscany, Italy, 56126
        • Azienda Ospedaliero Universitaria Pisana
    • Veneto
      • Padova, Veneto, Italy, 35128
        • Istituto Oncologico Veneto IRCCS
  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 HX
        • Maastricht UMC+
  • Norway
      • Oslo, Norway, 0450
        • Oslo Universitetssykehus Ullevål
  • Poland
      • Brzozów, Poland, 36-200
        • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza
    • Greater Poland Voivodeship
      • Konin, Greater Poland Voivodeship, Poland, 62-500
        • Przychodnia Lekarska KOMED
  • Slovakia
      • Bratislava, Slovakia, 833 10
        • Narodny onkologicky ustav
  • Spain
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46014
        • Hospital General Universitario de Valencia
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • A Coruña [LA Coruña]
      • Santiago de Compostela, A Coruña [LA Coruña], Spain, 15706
        • CHUS - Hospital Clinico Universitario
    • Barcelona [barcelona]
      • Barcelona, Barcelona [barcelona], Spain, 08035
        • Hospital Universitari Vall d'Hebron
    • Catalunya [cataluña]
      • Barcelona, Catalunya [cataluña], Spain, 08036
        • Hospital Clinic de Barcelona
      • L'Hospitalet de Llobregat, Catalunya [cataluña], Spain, 08908
        • Institut Català d'Oncologia - L'Hospitalet
    • Madrid, Comunidad de
      • Madrid, Madrid, Comunidad de, Spain, 28034
        • Hospital Universitario Ramon y Cajal
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
        • Heartlands Hospital
    • Aberdeen CITY
      • Aberdeen, Aberdeen CITY, United Kingdom, AB25 2ZN
        • Aberdeen Royal Infirmary
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Building - Phoenix
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic
    • Florida
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Cancer Center
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • The West Clinic, PLLC dba West Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: encorafenib, cetuximab and pembrolizumab
Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
Drug: Encorafenib
capsule
Other Names:
  • PF-07263896 LGX818 ONO-7702 W0090
Biological: Cetuximab
IV
Other Names:
  • Erbitux
Biological: Pembrolizumab
IV
Other Names:
  • Keytruda®, MK-3475
Active Comparator: Arm B: pembrolizumab
Participants receive pembrolizumab IV.
Biological: Pembrolizumab
IV
Other Names:
  • Keytruda®, MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: 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:
Duration of study, approximately 45 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: 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)
Duration of study, approximately 45 months
Overall Survival (OS)
Time Frame: 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)
Duration of study, approximately 45 months
Objective Response (OR)
Time Frame: 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)
Duration of study, approximately 45 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Collaborators

Eli Lilly and Company
Merck Sharp & Dohme LLC
Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 11, 2022

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

January 26, 2027

Study Registration Dates

First Submitted

January 19, 2022

First Submitted That Met QC Criteria

January 19, 2022

First Posted (Actual)

February 1, 2022

Study Record Updates

Last Update Posted (Actual)

April 7, 2026

Last Update Submitted That Met QC Criteria

April 6, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C4221022
  • SEAMARK (Other Identifier: Alias Study Number)
  • MK-3475-D31 (Other Identifier: Merck)
  • KEYNOTE-D31 (Other Identifier: Merck)
  • 2024-512119-34-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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