Clinical trial NCT05217446: A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
name: Merck KGaA, Darmstadt, Germany
name: Eli Lilly and Company
First posted: 2022-02-01
Enrollment: 107
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Duration of study, approximately 45 months
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: Duration of study, approximately 45 months
measure: Overall Survival (OS)
timeFrame: Duration of study, approximately 45 months
measure: Objective Response (OR)
timeFrame: Duration of study, approximately 45 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Building - Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Los Angeles
country: United States
facility: LAC USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center / Investigational Drug Services
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: Keck Hospital of USC Pasadena
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Cancer Center
state: Florida
city: Germantown
country: United States
facility: The West Clinic, PLLC dba West Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Bonheiden
country: Belgium
facility: Imelda General Hospital
state: Antwerpen
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
state: Bruxelles-capitale, Région DE
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
state: Bruxelles-capitale, Région DE
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences - Odette Cancer Centre
state: Ontario
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Center
state: Saskatchewan
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
state: Hradec Králové
city: Prague
country: Czechia
facility: Fakultni Thomayerova nemocnice
state: Praha 4
city: Prague
country: Czechia
facility: Fakultni nemocnice Bulovka
state: Praha 8
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: Hovedstaden
city: Copenhagen
country: Denmark
facility: Herlev and Gentofte Hospital
state: Hovedstaden
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital, Syd
state: Nordjylland
city: Vejle
country: Denmark
facility: Vejle Sygehus
state: Syddanmark
city: Paris Cedex 15
country: France
facility: Hôpital Européen Georges Pompidou
state: Paris
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire Estaing
city: Montpellier Cedex 5
country: France
facility: Institut Regional du Cancer de Montpellier - ICM Val d'Aurelle
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Muenchen
country: Germany
facility: Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
state: Bayern
city: Hamburg
country: Germany
facility: Facharztzentrum Eppendorf
city: Monserrato
country: Italy
facility: Policlinico Universitario Monserrato
state: Cagliari
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" Piazza Luigi Miraglia, 2 Napoli
state: Campania
city: Guastalla
country: Italy
facility: Ospedale di Guastalla
state: Emilia-romagna
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
state: Foggia
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: Milano
city: Candiolo
country: Italy
facility: Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
state: Torino
city: Livorno
country: Italy
facility: Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno
state: Toscana
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
state: Veneto
city: Brescia
country: Italy
facility: Fondazione Poliambulanza Istituto Ospedaliero
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
state: Limburg
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Ullevål
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED
state: Wielkopolskie
city: Brzozow
country: Poland
facility: Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario
state: A Coruña [LA Coruña]
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalunya [cataluña]
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia - L'Hospitalet
state: Catalunya [cataluña]
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Madrid, Comunidad DE
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Aberdeen CITY
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: