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


About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

- 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

- 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).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 5/2/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Zhaohui Jin, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Christina Wu, M.B., B.Ch., M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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