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

Phase 2

Active, not recruiting

• Conditions: Metastatic Colorectal Cancer
• Interventions: Biological: Pembrolizumab; Drug: Encorafenib; Biological: Cetuximab

• Registration Number: NCT05217446
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-19
• Study First Submitted QC: 2022-01-19
• Study First Posted: 2022-02-01
• Study Start: 2022-07-11
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-26
• Last Update Posted: 2025-06-29
• Primary Completion: 2026-03-28
• Study Completion: 2027-03-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 107

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: pembrolizumab	Pembrolizumab	Participants receive pembrolizumab IV.
Arm A: encorafenib, cetuximab and pembrolizumab	Cetuximab	Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
Arm A: encorafenib, cetuximab and pembrolizumab	Pembrolizumab	Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
Arm A: encorafenib, cetuximab and pembrolizumab	Encorafenib	Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	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 Outcome Measures

Name	Time	Method
Incidence of adverse events	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)
Overall Survival (OS)	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)
Objective Response (OR)	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)

Trial Locations

Locations (64)

Mayo Clinic Building - Phoenix; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic; 🇺🇸 Scottsdale, Arizona, 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 / Investigational Drug Services; 🇺🇸 Los Angeles, California, United States

USC/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Keck Hospital of USC Pasadena; 🇺🇸 Pasadena, California, United States

Scroll for more (54 remaining)