The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

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Gastrointestinal Cancer

Encorafenib

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
Phase 2
NCT05217446

Active enrolling

Globe
Locations

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

Study design

Participant Group/Arm

EXPERIMENTAL: Arm A: encorafenib, cetuximab and pembrolizumab

Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.

Intervention/Treatment

DRUG: Encorafenib

capsule

BIOLOGICAL: Cetuximab

IV

BIOLOGICAL: Pembrolizumab

IV

Participant Group/Arm

ACTIVE_COMPARATOR: Arm B: pembrolizumab

Participants receive pembrolizumab IV.

Intervention/Treatment

BIOLOGICAL: Pembrolizumab

IV

Key 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).

Key dates

Study start date
  • July 2022
Estimated primary completion date
  • March 2027

Key endpoints

Primary Outcome Measures
Outcome Measure

Progression-free Survival (PFS)

Measure Description

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:

Time Frame

Duration of study, approximately 45 months

Secondary Outcome Measures:
Outcome Measure

Incidence of adverse events

Measure Description

Incidence and severity of AEs graded according to the NCI CTCAE v4.03: encorafenib and cetuximab + pembrolizumab (Arm A) vs pembrolizumab (Arm B)

Time Frame

Duration of study, approximately 45 months

Outcome Measure

Overall Survival (OS)

Measure Description

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)

Time Frame

Duration of study, approximately 45 months

Outcome Measure

Objective Response (OR)

Measure Description

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)

Time Frame

Duration of study, approximately 45 months

Number of participants

104

Collaborators and investigators

Sponsor: Pfizer

Collaborator: Merck Sharp & Dohme LLC, Merck KGaA, Darmstadt, Germany, Eli Lilly and Company

This information is current as of April 30th 2024.