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

NCT05217446 | Active Not Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: C4221022SEAMARK2024-512119-34-00KEYNOTE-D31MK-3475-D31
• Study Type: interventional
• Target: 107
• Locations: 15 countries
• Sites: 59

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.

Conditions

Metastatic Colorectal Cancer

Keywords

Keynote-D31; BRAF V600E mutation positive; Colon cancer; Rectal cancer; Metastatic colon cancer; Colon cancer BRAF; Rectal cancer BRAF; MSI-H colorectal cancer; MSI-H colon cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  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 Outcomes (3)

• Incidence of adverse events

  Duration of study, approximately 45 months

• Overall Survival (OS)

  Duration of study, approximately 45 months

• Objective Response (OR)

  Duration of study, approximately 45 months

Study Arms (2)

Arm A: encorafenib, cetuximab and pembrolizumab

EXPERIMENTAL

Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.

Drug: Encorafenib; Biological: Cetuximab; Biological: Pembrolizumab

Arm B: pembrolizumab

ACTIVE COMPARATOR

Participants receive pembrolizumab IV.

Biological: Pembrolizumab

Interventions

Encorafenib DRUG

capsule

Also known as: PF-07263896 LGX818 ONO-7702 W0090

Arm A: encorafenib, cetuximab and pembrolizumab

Cetuximab BIOLOGICAL

IV

Also known as: Erbitux

Arm A: encorafenib, cetuximab and pembrolizumab

Pembrolizumab BIOLOGICAL

IV

Also known as: Keytruda®, MK-3475

Arm A: encorafenib, cetuximab and pembrolizumab; Arm B: pembrolizumab

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead
• Merck Sharp & Dohme LLC: collaborator
• Merck KGaA, Darmstadt, Germany: collaborator
• Eli Lilly and Company: collaborator

Study Sites (59)

Mayo Clinic Building - Phoenix

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Mount Sinai Cancer Center

Miami Beach, Florida, 33140, United States

Location

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee, 38138, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3052, Australia

Location

Imelda General Hospital

Bonheiden, Antwerpen, 2820, Belgium

Location

Institut Jules Bordet

Anderlecht, Bruxelles-capitale, Région de, 1070, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, Bruxelles-capitale, Région de, 1200, Belgium

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences - Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Saskatoon City Hospital

Saskatoon, Saskatchewan, S7K 0M7, Canada

Location

Saskatoon Cancer Center

Saskatoon, Saskatchewan, S7N4H4, Canada

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, Hradec Králové, 500 05, Czechia

Location

Fakultni Thomayerova nemocnice

Prague, Praha 4, 14059, Czechia

Location

Fakultni nemocnice Bulovka

Prague, Praha 8, 180 81, Czechia

Location

Rigshospitalet

Copenhagen, Capital Region, 2100, Denmark

Location

Herlev and Gentofte Hospital

Copenhagen, Capital Region, 2730, Denmark

Location

Aalborg Universitetshospital, Syd

Aalborg, North Denmark, 9000, Denmark

Location

Vejle Hospital, Department of Oncology

Vejle, Region Syddanmark, 7100, Denmark

Location

Vejle Sygehus

Vejle, Region Syddanmark, 7100, Denmark

Location

Hôpital Européen Georges Pompidou

Paris, Paris, 75015, France

Location

Centre Hospitalier Universitaire Estaing

Clermont-Ferrand, 63100, France

Location

CHU Estaing

Clermont-Ferrand, 63100, France

Location

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

Montpellier, 34298, France

Location

Hôpital Saint Antoine

Paris, 75571, France

Location

Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie

Munich, Bavaria, 81737, Germany

Location

Facharztzentrum Eppendorf

Hamburg, 20249, Germany

Location

Policlinico Universitario Monserrato

Monserrato, Cagliari, 09042, Italy

Location

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

Naples, Campania, 80131, Italy

Location

Ospedale di Guastalla

Guastalla, Emilia-Romagna, 42016, Italy

Location

IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, 71013, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Milano, 20162, Italy

Location

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

Candiolo, Torino, 10060, Italy

Location

Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno

Livorno, Tuscany, 57124, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, 56126, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, Veneto, 35128, Italy

Location

Fondazione Poliambulanza Istituto Ospedaliero

Brescia, 25124, Italy

Location

Istituto Europeo di Oncologia IRCCS

Milan, 20141, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, 42123, Italy

Location

Maastricht UMC+

Maastricht, Limburg, 6229 HX, Netherlands

Location

Oslo Universitetssykehus Ullevål

Oslo, 0450, Norway

Location

Przychodnia Lekarska KOMED

Konin, Greater Poland Voivodeship, 62-500, Poland

Location

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

Brzozów, 36-200, Poland

Location

Narodny onkologicky ustav

Bratislava, 833 10, Slovakia

Location

CHUS - Hospital Clinico Universitario

Santiago de Compostela, A Coruña [LA Coruña], 15706, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona], 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Catalunya [cataluña], 08036, Spain

Location

Institut Català d'Oncologia - L'Hospitalet

L'Hospitalet de Llobregat, Catalunya [cataluña], 08908, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Comunidad de, 28034, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Aberdeen Royal Infirmary

Aberdeen, Aberdeen CITY, AB25 2ZN, United Kingdom

Location

Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37815847 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

encorafenib; Cetuximab; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: January 19, 2022
• First Posted: February 1, 2022
• Study Start: July 11, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 26, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (5); NL (1); US (6); PL (2); NO (1); AU (3); FR (5); ES (9); GB (2); BE (3); CZ (3); IT (12); CA (4); DE (2); SL (1)