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

March 20, 2024 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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

104

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 Contact

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Recruiting
        • Chris O'Brien Lifehouse
      • St Leonards, New South Wales, Australia, 2065
        • Recruiting
        • GenesisCare North Shore
    • Queensland
      • Brisbane, Queensland, Australia, 4120
        • Recruiting
        • Gallipoli Medical Research Foundation
      • Greenslopes, Queensland, Australia, 4120
        • Recruiting
        • Greenslopes Private Hospital
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Recruiting
        • Austin Health
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Peter MacCallum Cancer Centre
      • Parkville, Victoria, Australia, 3052
        • Recruiting
        • Royal Melbourne Hospital
  • Belgium
      • Antwerpen, Belgium, 2020
        • Recruiting
        • ZNA Middelheim
    • Antwerpen
      • Bonheiden, Antwerpen, Belgium, 2820
        • Recruiting
        • Imelda General Hospital
    • Bruxelles-capitale, Région DE
      • Anderlecht, Bruxelles-capitale, Région DE, Belgium, 1070
        • Recruiting
        • Institut Jules Bordet
      • Brussels, Bruxelles-capitale, Région DE, Belgium, 1200
        • Recruiting
        • Cliniques Universitaires Saint-Luc
    • Oost-vlaanderen
      • Gent, Oost-vlaanderen, Belgium, 9000
        • Recruiting
        • UZ Gent
    • Vlaams-brabant
      • Leuven, Vlaams-brabant, Belgium, 3000
        • Recruiting
        • UZ Leuven
  • Canada
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • Recruiting
        • William Osler Health System
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recruiting
        • The Ottawa Hospital - General Campus
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Health Sciences - Odette Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, h1t2m4
        • Recruiting
        • CIUSSS de l'Est-de-l'Île-de-Montréal
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N4H4
        • Recruiting
        • Saskatoon Cancer Center
  • Czechia
    • Hradec Králové
      • Hradec Kralove, Hradec Králové, Czechia, 500 05
        • Recruiting
        • Fakultni nemocnice Hradec Kralove
    • Olomoucký KRAJ
      • Olomouc, Olomoucký KRAJ, Czechia, 779 00
        • Recruiting
        • Fakultní Nemocnice Olomouc
    • Praha 4
      • Prague, Praha 4, Czechia, 14059
        • Recruiting
        • Fakultni Thomayerova nemocnice
    • Praha 8
      • Prague, Praha 8, Czechia, 180 81
        • Recruiting
        • Fakultni nemocnice Bulovka
  • Denmark
    • Hovedstaden
      • Copenhagen, Hovedstaden, Denmark, 2100
        • Recruiting
        • Rigshospitalet
      • Copenhagen, Hovedstaden, Denmark, 2730
        • Recruiting
        • Herlev and Gentofte Hospital
    • Nordjylland
      • Aalborg, Nordjylland, Denmark, 9000
        • Recruiting
        • Aalborg Universitetshospital, Syd
    • Syddanmark
      • Vejle, Syddanmark, Denmark, 7100
        • Recruiting
        • Vejle Sygehus
  • France
      • Clermont Ferrand, France, 63100
        • Recruiting
        • CHU Estaing
      • Clermont-Ferrand, France, 63100
        • Recruiting
        • Centre Hospitalier Universitaire Estaing
      • Montpellier, France, 34298
        • Recruiting
        • Institut régional du Cancer Montpellier
      • Montpellier Cedex 5, France, 34298
        • Recruiting
        • Institut régional du Cancer de Montpellier - ICM Val d'Aurelle
      • Paris, France, 75571
        • Recruiting
        • Hopital Saint Antoine
    • Paris
      • Paris Cedex 15, Paris, France, 75015
        • Recruiting
        • Hôpital Européen Georges Pompidou
  • Germany
      • Berlin, Germany, 10707
        • Recruiting
        • Onkologische Schwerpunktpraxis Kurfuerstendamm
      • Halle /Saale, Germany, 06108
        • Recruiting
        • Studiengesellschaft BSF UG
      • Hamburg, Germany, 20249
        • Recruiting
        • Facharztzentrum Eppendorf
    • Bayern
      • Muenchen, Bayern, Germany, 81737
        • Recruiting
        • Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
    • Hessen
      • Frankfurt, Hessen, Germany, 60488
        • Recruiting
        • Institut für Klinisch Onkologische Forschung
    • Niedersachsen
      • Oldenburg, Niedersachsen, Germany, 26133
        • Recruiting
        • Klinikum Oldenburg
    • Sachsen
      • Leipzig, Sachsen, Germany, 04103
        • Recruiting
        • Universitätsklinikum Leipzig
    • Sachsen-anhalt
      • Halle (Saale), Sachsen-anhalt, Germany, 06108
        • Recruiting
        • Studiengesellschaft BSF Unternehmergesellschaft
  • Italy
      • Brescia, Italy, 25124
        • Recruiting
        • Fondazione Poliambulanza Istituto Ospedaliero
      • Milano, Italy, 20141
        • Recruiting
        • Istituto Europeo di Oncologia IRCCS
      • Reggio Emilia, Italy, 42123
        • Recruiting
        • Arcispedale Santa Maria Nuova
    • Cagliari
      • Monserrato, Cagliari, Italy, 09042
        • Recruiting
        • Policlinico Universitario Monserrato
    • Campania
      • Napoli, Campania, Italy, 80131
        • Recruiting
        • Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" Piazza Luigi Miraglia, 2 Napoli
    • Emilia-romagna
      • Guastalla, Emilia-romagna, Italy, 42016
        • Recruiting
        • Ospedale di Guastalla
    • Foggia
      • San Giovanni Rotondo, Foggia, Italy, 71013
        • Recruiting
        • IRCCS Casa Sollievo della Sofferenza
    • Milano
      • Milan, Milano, Italy, 20162
        • Recruiting
        • Asst Grande Ospedale Metropolitano Niguarda
    • Torino
      • Candiolo, Torino, Italy, 10060
        • Recruiting
        • Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
    • Toscana
      • Livorno, Toscana, Italy, 57124
        • Recruiting
        • Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno
      • Pisa, Toscana, Italy, 56126
        • Recruiting
        • Azienda Ospedaliero Universitaria Pisana
    • Veneto
      • Padova, Veneto, Italy, 35128
        • Recruiting
        • Istituto Oncologico Veneto IRCCS
  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 HX
        • Recruiting
        • Maastricht UMC+
    • Zuid-holland
      • Leidschendam, Zuid-holland, Netherlands, 2262 BA
        • Recruiting
        • Haaglanden MC - locatie Antoniushove
  • Norway
      • Oslo, Norway, 0450
        • Recruiting
        • Oslo Universitetssykehus Ullevål
    • Sør-trøndelag
      • Trondheim, Sør-trøndelag, Norway, 7030
        • Recruiting
        • St. Olavs Hospital
  • Poland
      • Brzozow, Poland, 36-200
        • Recruiting
        • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza
      • Bytom, Poland, 41-902
        • Recruiting
        • SPZOZ Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu
      • Gdansk, Poland, 80-219
        • Recruiting
        • Copernicus Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii
      • Radom, Poland, 26-600
        • Recruiting
        • Radomskie Centrum Onkologii im. Bohaterow Radomskiego Czerwca 76
    • Wielkopolskie
      • Konin, Wielkopolskie, Poland, 62-500
        • Recruiting
        • Przychodnia Lekarska KOMED
  • Slovakia
      • Banska Bystrica, Slovakia, 975 17
        • Recruiting
        • Fakultna nemocnica s poliklinikou F. D. Roosevelta Banska Bystrica
      • Bratislava, Slovakia, 833 10
        • Recruiting
        • Narodny onkologicky ustav
      • Bratislava, Slovakia, 812 50
        • Recruiting
        • Onkologicky ustav sv. Alzbety, s.r.o.
      • Kosice, Slovakia, 04191
        • Recruiting
        • Vychodoslovensky onkologicky ustav, a.s.
  • Spain
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28007
        • Recruiting
        • Hospital General Universitario Gregorio Marañon
      • Sevilla, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen Del Rocio
      • Valencia, Spain, 46014
        • Recruiting
        • Hospital General Universitario de Valencia
      • Zaragoza, Spain, 50009
        • Recruiting
        • Hospital Universitario Miguel Servet
    • A Coruña [LA Coruña]
      • Santiago de Compostela, A Coruña [LA Coruña], Spain, 15706
        • Recruiting
        • CHUS - Hospital Clinico Universitario
    • Alicante
      • Elche, Alicante, Spain, 03202
        • Recruiting
        • Hospital General Universitario de Elche
    • Barcelona [barcelona]
      • Barcelona, Barcelona [barcelona], Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
    • Catalunya [cataluña]
      • Barcelona, Catalunya [cataluña], Spain, 08036
        • Recruiting
        • Hospital Clinic de Barcelona
      • L'Hospitalet de Llobregat, Catalunya [cataluña], Spain, 08908
        • Recruiting
        • Institut Català d'Oncologia - L'Hospitalet
    • Madrid, Comunidad DE
      • Madrid, Madrid, Comunidad DE, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon Y Cajal
      • Madrid, Madrid, Comunidad DE, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
  • Sweden
      • Skövde, Sweden, 541 85
        • Recruiting
        • Skaraborgs sjukhus Skövde
    • Stockholms LÄN [se-01]
      • Solna, Stockholms LÄN [se-01], Sweden, 171 64
        • Recruiting
        • Karolinska Universitetssjukhuset Solna
      • Stockholm, Stockholms LÄN [se-01], Sweden, 11883
        • Recruiting
        • Södersjukhuset
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
        • Recruiting
        • Heartlands Hospital
    • Aberdeen CITY
      • Aberdeen, Aberdeen CITY, United Kingdom, AB25 2ZN
        • Recruiting
        • Aberdeen Royal Infirmary
    • England
      • London, England, United Kingdom, SE1 9RT
        • Recruiting
        • Guy's & St Thomas's NHS Foundation Trust
    • London, CITY OF
      • London, London, CITY OF, United Kingdom, SE1 9RT
        • Recruiting
        • Guy's & St Thomas' NHS Foundation Trust
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Hospital
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Building - Phoenix
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC/Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Keck Hospital of USC
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC/Norris Comprehensive Cancer Center / Investigational Drug Services
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Keck School of Medicine of USC
      • Los Angeles, California, United States, 90033
        • Recruiting
        • LAC USC Medical Center
      • Pasadena, California, United States, 91105
        • Recruiting
        • Keck Hospital of USC Pasadena
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Hospital and Clinics, Sylvester Cancer Center
      • Miami Beach, Florida, United States, 33140
        • Recruiting
        • Mount Sinai Cancer Center
      • Plantation, Florida, United States, 33324
        • Recruiting
        • University of Miami Hospital and Clinics, Sylvester Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Cancer Center Outpatient Pharmacy
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Recruiting
        • The West Clinic, PLLC dba West Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • 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.

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)

March 28, 2026

Study Completion (Estimated)

March 28, 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)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 20, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C4221022
  • 2021-003715-26 (EudraCT Number)
  • SEAMARK (Other Identifier: Alias Study Number)
  • MK-3475-D31 (Other Identifier: Merck)
  • KEYNOTE-D31 (Other Identifier: Merck)

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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