---
title: A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
nct_id: NCT05217446
overall_status: ACTIVE_NOT_RECRUITING
phase: PHASE2
sponsor: Pfizer
study_type: INTERVENTIONAL
primary_condition: Metastatic Colorectal Cancer
countries: United States, Australia, Belgium, Canada, Czechia, Denmark, France, Germany, Italy, Netherlands, Norway, Poland, Slovakia, Spain, United Kingdom
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT05217446.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT05217446"
ct_last_update_post_date: 2026-04-07
last_seen_at: "2026-05-12T06:14:54.085Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# 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

**NCT ID:** [NCT05217446](https://clinicaltrials.gov/study/NCT05217446)

## Key Facts

- **Status:** ACTIVE_NOT_RECRUITING
- **Phase:** PHASE2
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 107
- **Lead Sponsor:** Pfizer
- **Collaborators:** Merck Sharp & Dohme LLC, Merck KGaA, Darmstadt, Germany, Eli Lilly and Company
- **Conditions:** Metastatic Colorectal Cancer
- **Start Date:** 2022-07-11
- **Completion Date:** 2027-01-26
- **CT.gov Last Update:** 2026-04-07

## 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

- **Minimum age:** 16 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
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).
```

## Arms

- **Arm A: encorafenib, cetuximab and pembrolizumab** (EXPERIMENTAL) — Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
- **Arm B: pembrolizumab** (ACTIVE_COMPARATOR) — Participants receive pembrolizumab IV.

## Interventions

- **Encorafenib** (DRUG) — capsule
- **Cetuximab** (BIOLOGICAL) — IV
- **Pembrolizumab** (BIOLOGICAL) — IV

## Primary Outcomes

- **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:

## Secondary Outcomes

- **Incidence of adverse events** _(time frame: Duration of study, approximately 45 months)_
- **Overall Survival (OS)** _(time frame: Duration of study, approximately 45 months)_
- **Objective Response (OR)** _(time frame: Duration of study, approximately 45 months)_

## Locations (59)

- Mayo Clinic Building - Phoenix, Phoenix, Arizona, United States
- Mayo Clinic Hospital, Phoenix, Arizona, United States
- Mayo Clinic, Scottsdale, Arizona, United States
- Mount Sinai Cancer Center, Miami Beach, Florida, United States
- The West Clinic, PLLC dba West Cancer Center, Germantown, Tennessee, United States
- MD Anderson Cancer Center, Houston, Texas, United States
- Austin Health, Heidelberg, Victoria, Australia
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Royal Melbourne Hospital, Parkville, Victoria, Australia
- Imelda General Hospital, Bonheiden, Antwerpen, Belgium
- Institut Jules Bordet, Anderlecht, Bruxelles-capitale, Région de, Belgium
- Cliniques universitaires Saint-Luc, Brussels, Bruxelles-capitale, Région de, Belgium
- The Ottawa Hospital - General Campus, Ottawa, Ontario, Canada
- Sunnybrook Health Sciences - Odette Cancer Centre, Toronto, Ontario, Canada
- Saskatchewan Health Authority, Saskatoon, Saskatchewan, Canada
- Saskatoon Cancer Center, Saskatoon, Saskatchewan, Canada
- Fakultni nemocnice Hradec Kralove, Hradec Králové, Hradec Králové, Czechia
- Fakultni Thomayerova nemocnice, Prague, Praha 4, Czechia
- Fakultni nemocnice Bulovka, Prague, Praha 8, Czechia
- Rigshospitalet, Copenhagen, Capital Region, Denmark
- Herlev and Gentofte Hospital, Copenhagen, Capital Region, Denmark
- Aalborg Universitetshospital, Syd, Aalborg, North Denmark, Denmark
- Vejle Hospital, Department of Oncology, Vejle, Region Syddanmark, Denmark
- Vejle Sygehus, Vejle, Region Syddanmark, Denmark
- Hôpital Européen Georges Pompidou, Paris, Paris, France
- Centre Hospitalier Universitaire Estaing, Clermont-Ferrand, France
- CHU Estaing, Clermont-Ferrand, France
- Institut Regional du Cancer de Montpellier - ICM Val d'Aurelle, Montpellier, France
- Hôpital Saint Antoine, Paris, France
- Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie, Munich, Bavaria, Germany
- Facharztzentrum Eppendorf, Hamburg, Germany
- Policlinico Universitario Monserrato, Monserrato, Cagliari, Italy
- Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" Piazza Luigi Miraglia, 2 Napoli, Naples, Campania, Italy
- Ospedale di Guastalla, Guastalla, Emilia-Romagna, Italy
- IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
- ASST Grande Ospedale Metropolitano Niguarda, Milan, Milano, Italy
- Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia, Candiolo, Torino, Italy
- Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno, Livorno, Tuscany, Italy
- Azienda Ospedaliero Universitaria Pisana, Pisa, Tuscany, Italy
- Istituto Oncologico Veneto IRCCS, Padova, Veneto, Italy
- Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
- Istituto Europeo di Oncologia IRCCS, Milan, Italy
- Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
- Maastricht UMC+, Maastricht, Limburg, Netherlands
- Oslo Universitetssykehus Ullevål, Oslo, Norway
- Przychodnia Lekarska KOMED, Konin, Greater Poland Voivodeship, Poland
- Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza, Brzozów, Poland
- Narodny onkologicky ustav, Bratislava, Slovakia
- CHUS - Hospital Clinico Universitario, Santiago de Compostela, A Coruña [LA Coruña], Spain
- Hospital Universitari Vall d'Hebron, Barcelona, Barcelona [barcelona], Spain
- Hospital Clínic de Barcelona, Barcelona, Catalunya [cataluña], Spain
- Institut Català d'Oncologia - L'Hospitalet, L'Hospitalet de Llobregat, Catalunya [cataluña], Spain
- Hospital Universitario Ramón y Cajal, Madrid, Madrid, Comunidad de, Spain
- Hospital General Universitario Gregorio Marañon, Madrid, Spain
- Hospital Universitario Virgen Del Rocio, Seville, Spain
- Hospital General Universitario de Valencia, Valencia, Spain
- Hospital Universitario Miguel Servet, Zaragoza, Spain
- Aberdeen Royal Infirmary, Aberdeen, Aberdeen CITY, United Kingdom
- Heartlands Hospital, Birmingham, United Kingdom

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `sponsor.collaborators` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.mayo clinic building - phoenix|phoenix|arizona|united states` — added _(2026-05-12)_
- `locations.mayo clinic hospital|phoenix|arizona|united states` — added _(2026-05-12)_
- `locations.mayo clinic|scottsdale|arizona|united states` — added _(2026-05-12)_
- `locations.mount sinai cancer center|miami beach|florida|united states` — added _(2026-05-12)_
- `locations.the west clinic, pllc dba west cancer center|germantown|tennessee|united states` — added _(2026-05-12)_
- `locations.md anderson cancer center|houston|texas|united states` — added _(2026-05-12)_
- `locations.austin health|heidelberg|victoria|australia` — added _(2026-05-12)_
- `locations.peter maccallum cancer centre|melbourne|victoria|australia` — added _(2026-05-12)_
- `locations.royal melbourne hospital|parkville|victoria|australia` — added _(2026-05-12)_
- `locations.imelda general hospital|bonheiden|antwerpen|belgium` — added _(2026-05-12)_
- `locations.institut jules bordet|anderlecht|bruxelles-capitale, région de|belgium` — added _(2026-05-12)_
- `locations.cliniques universitaires saint-luc|brussels|bruxelles-capitale, région de|belgium` — added _(2026-05-12)_
- `locations.the ottawa hospital - general campus|ottawa|ontario|canada` — added _(2026-05-12)_
- `locations.sunnybrook health sciences - odette cancer centre|toronto|ontario|canada` — added _(2026-05-12)_
- `locations.saskatchewan health authority|saskatoon|saskatchewan|canada` — added _(2026-05-12)_
- `locations.saskatoon cancer center|saskatoon|saskatchewan|canada` — added _(2026-05-12)_
- `locations.fakultni nemocnice hradec kralove|hradec králové|hradec králové|czechia` — added _(2026-05-12)_
- `locations.fakultni thomayerova nemocnice|prague|praha 4|czechia` — added _(2026-05-12)_
- `locations.fakultni nemocnice bulovka|prague|praha 8|czechia` — added _(2026-05-12)_
- `locations.rigshospitalet|copenhagen|capital region|denmark` — added _(2026-05-12)_
- `locations.herlev and gentofte hospital|copenhagen|capital region|denmark` — added _(2026-05-12)_
- `locations.aalborg universitetshospital, syd|aalborg|north denmark|denmark` — added _(2026-05-12)_
- `locations.vejle hospital, department of oncology|vejle|region syddanmark|denmark` — added _(2026-05-12)_
- `locations.vejle sygehus|vejle|region syddanmark|denmark` — added _(2026-05-12)_
- `locations.hôpital européen georges pompidou|paris|paris|france` — added _(2026-05-12)_
- `locations.centre hospitalier universitaire estaing|clermont-ferrand||france` — added _(2026-05-12)_
- `locations.chu estaing|clermont-ferrand||france` — added _(2026-05-12)_
- `locations.institut regional du cancer de montpellier - icm val d'aurelle|montpellier||france` — added _(2026-05-12)_
- `locations.hôpital saint antoine|paris||france` — added _(2026-05-12)_
- `locations.muenchen klinik neuperlach, klinik fuer haematologie und onkologie|munich|bavaria|germany` — added _(2026-05-12)_
- `locations.facharztzentrum eppendorf|hamburg||germany` — added _(2026-05-12)_
- `locations.policlinico universitario monserrato|monserrato|cagliari|italy` — added _(2026-05-12)_
- `locations.azienda ospedaliera universitaria dell'università "luigi vanvitelli" piazza luigi miraglia, 2 napoli|naples|campania|italy` — added _(2026-05-12)_
- `locations.ospedale di guastalla|guastalla|emilia-romagna|italy` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT05217446.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT05217446*  
*This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*