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

Metastatic Colorectal Cancer Clinical Trial

— SEAMARK  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05217446
• Other study ID #: C4221022
• Secondary ID: 2021-003715-26SE
• Status: Recruiting
• Phase: Phase 2
• Start date: July 11, 2022
• Est. completion date: March 28, 2027

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: March 28, 2027
• Est. primary completion date: March 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Encorafenib
capsule

Biological:
• Cetuximab
IV
• Pembrolizumab
IV

Locations

Country	Name	City	State
Australia	Gallipoli Medical Research Foundation	Brisbane	Queensland
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Greenslopes Private Hospital	Greenslopes	Queensland
Australia	Austin Health	Heidelberg	Victoria
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	GenesisCare North Shore	St Leonards	New South Wales
Belgium	Institut Jules Bordet	Anderlecht	Bruxelles-capitale, Région DE
Belgium	ZNA Middelheim	Antwerpen
Belgium	Imelda General Hospital	Bonheiden	Antwerpen
Belgium	Cliniques universitaires Saint-Luc	Brussels	Bruxelles-capitale, Région DE
Belgium	UZ Gent	Gent	Oost-vlaanderen
Belgium	UZ Leuven	Leuven	Vlaams-brabant
Canada	William Osler Health System	Brampton	Ontario
Canada	CIUSSS de l'Est-de-l'Île-de-Montréal	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Saskatoon Cancer Center	Saskatoon	Saskatchewan
Canada	Sunnybrook Health Sciences - Odette Cancer Centre	Toronto	Ontario
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove	Hradec Králové
Czechia	Fakultni nemocnice Olomouc	Olomouc	Olomoucký KRAJ
Czechia	Fakultni nemocnice Bulovka	Prague	Praha 8
Czechia	Fakultni Thomayerova nemocnice	Prague	Praha 4
Denmark	Aalborg Universitetshospital, Syd	Aalborg	Nordjylland
Denmark	Herlev and Gentofte Hospital	Copenhagen	Hovedstaden
Denmark	Rigshospitalet	Copenhagen	Hovedstaden
Denmark	Vejle Sygehus	Vejle	Syddanmark
France	CHU Estaing	Clermont Ferrand
France	Centre Hospitalier Universitaire Estaing	Clermont-Ferrand
France	Institut Régional du Cancer Montpellier	Montpellier
France	Institut Regional du Cancer de Montpellier - ICM Val d'Aurelle	Montpellier Cedex 5
France	Hôpital Saint Antoine	Paris
France	Hôpital Européen Georges Pompidou	Paris Cedex 15	Paris
Germany	Onkologische Schwerpunktpraxis Kurfuerstendamm	Berlin
Germany	Institut für Klinisch Onkologische Forschung	Frankfurt	Hessen
Germany	Studiengesellschaft BSF Unternehmergesellschaft	Halle (Saale)	Sachsen-anhalt
Germany	Studiengesellschaft BSF UG	Halle /Saale
Germany	Facharztzentrum Eppendorf	Hamburg
Germany	Universitätsklinikum Leipzig	Leipzig	Sachsen
Germany	Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie	Muenchen	Bayern
Germany	Klinikum Oldenburg	Oldenburg	Niedersachsen
Italy	Fondazione Poliambulanza Istituto Ospedaliero	Brescia
Italy	Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia	Candiolo	Torino
Italy	Ospedale di Guastalla	Guastalla	Emilia-romagna
Italy	Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno	Livorno	Toscana
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milan	Milano
Italy	Istituto Europeo di Oncologia IRCCS	Milano
Italy	Policlinico Universitario Monserrato	Monserrato	Cagliari
Italy	Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" Piazza Luigi Miraglia, 2 Napoli	Napoli	Campania
Italy	Istituto Oncologico Veneto IRCCS	Padova	Veneto
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Netherlands	Haaglanden MC - locatie Antoniushove	Leidschendam	Zuid-holland
Netherlands	Maastricht UMC+	Maastricht	Limburg
Norway	Oslo Universitetssykehus Ullevål	Oslo
Norway	St. Olavs Hospital	Trondheim	Sør-trøndelag
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza	Brzozow
Poland	SPZOZ Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu	Bytom
Poland	Copernicus Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii	Gdansk
Poland	Przychodnia Lekarska KOMED	Konin	Wielkopolskie
Poland	Radomskie Centrum Onkologii im. Bohaterow Radomskiego Czerwca 76	Radom
Slovakia	Fakultna nemocnica s poliklinikou F. D. Roosevelta Banska Bystrica	Banska Bystrica
Slovakia	Narodny onkologicky ustav	Bratislava
Slovakia	Onkologicky ustav sv. Alzbety, s.r.o.	Bratislava
Slovakia	Vychodoslovensky onkologicky ustav, a.s.	Kosice
Spain	Hospital Clínic de Barcelona	Barcelona	Catalunya [cataluña]
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [barcelona]
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Institut Català d'Oncologia - L'Hospitalet	L'Hospitalet de Llobregat	Catalunya [cataluña]
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad DE
Spain	Hospital Universitario Ramón y Cajal	Madrid	Madrid, Comunidad DE
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela	A Coruña [LA Coruña]
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Skaraborgs Sjukhus Skövde	Skövde
Sweden	Karolinska Universitetssjukhuset Solna	Solna	Stockholms LÄN [se-01]
Sweden	Södersjukhuset	Stockholm	Stockholms LÄN [se-01]
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Aberdeen CITY
United Kingdom	Heartlands Hospital	Birmingham
United Kingdom	Guy's & St Thomas' NHS Foundation Trust	London	London, CITY OF
United Kingdom	Guy's & St Thomas's NHS Foundation Trust	London	England
United States	UChicago Medicine - River East	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	UChicago Medicine at Ingalls - Flossmoor	Flossmoor	Illinois
United States	The West Clinic, PLLC dba West Cancer Center	Germantown	Tennessee
United States	UChicago Medicine Ingalls Memorial	Harvey	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
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	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center / Investigational Drug Services	Los Angeles	California
United States	University of Miami Hospital and Clinics, Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Cancer Center	Miami Beach	Florida
United States	University of Chicago Comprehensive Cancer Center at Silver Cross Hospital	New Lenox	Illinois
United States	Columbia University Medical Center	New York	New York
United States	The University of Chicago Medicine Center of Advanced Care Orland Park	Orland Park	Illinois
United States	Keck Hospital of USC Pasadena	Pasadena	California
United States	Mayo Clinic Building - Phoenix	Phoenix	Arizona
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	University of Miami Hospital and Clinics, Sylvester Cancer Center	Plantation	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic Cancer Center Outpatient Pharmacy	Rochester	Minnesota
United States	Mayo Clinic	Scottsdale	Arizona
United States	UChicago Medicine at Ingalls - Tinley Park	Tinley Park	Illinois

Sponsors (4)

Lead Sponsor	Collaborator
Pfizer	Eli Lilly and Company, Merck KGaA, Darmstadt, Germany, Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of adverse events	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
Secondary	Overall Survival (OS)	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
Secondary	Objective Response (OR)	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

External Links

•   SEAMARK Study Webpage on PfizerClincialTrials.com
•   To obtain contact information for a study center near you, click here.