Encorafenib With Cetuximab and Nivolumab Induce Early Responses in MSS, BRAF V600E-Mutated Metastatic CRC


In a phase 1/2 study demonstrated that the combination of encorafenib, cetuximab, and nivolumab was well tolerated and led to responses in patients with microsatellite stable BRAFV600E metastatic colorectal cancer.

According to a presentation given by Van K. Morris, MD, encorafenib combined with cetuximab, and nivolumab (Opdivo) had a promising response profile and was well tolerated in patients with microsatellite stable (MSS) BRAFV600E metastatic colorectal cancer (CRC), according to results from a phase 1/2 trial (NCT04017650).

Results, which were presented at the 2022 Gastrointestinal Cancers Symposium, highlighted an overall response rate (ORR) of 50% (95% CI, 28%-72%) among those treated with the combination, with all patients achieving partial responses. The disease control rate (DCR) was 96% (95% CI, 77%-100%) among the 22 evaluable patients.

“Encorafenib, cetuximab, and nivolumab appears to be a safe and well-tolerated combination for patients with microsatellite stable BRAF-mutated metastatic CRC,” Morris, assistant professor of the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, explained in his presentation on the data. “The efficacy of this combination appears promising when considering the precedent of encorafenib and cetuximab alone from the previously reported BEACON study.”

Patients with MSS BRAFV600E metastatic CRC were eligible to enroll on the study. Further eligibility criteria required patients to have received 1 to 2 prior lines of systemic therapy and have an ECOG performance status of 1 or less. Prior treatment with a BRAF, MEK, ERK, anti-EGFR, or immune-checkpoint therapy was not allowed.

The primary end points of the phase 1/2 study were radiographic response per RECIST 1.1 criteria and safety. Key secondary end points included progression-free survival (PFS), overall survival (OS), duration of response, DCR, and time to response.

The study regimen included a 300 mg dose of oral encorafenib that was administered daily daily, 500 mg/m2 of cetuximab intravenously every 14 days, and 480 mg of nivolumab intravenously every 28 days.

A total of 26 patients were treated on protocol, with all of whom were evaluable for safety and 22 were evaluable for response. The median age for the full population was 58 years (range, 32-85). Most patients were female (58%), Caucasian (85%), and had right primary tumor sidedness (62%). Moreover, most patients had received 1 prior line of therapy (62%). Investigators reported an even split between those who had an ECOG performance status of 0 and 1.

Common any grade adverse effects (AEs) included headache (65%), nausea (35%), maculopapular rash (31%), arthralgia (27%), acneiform rash (27%), chills (23%), and precancerous skin lesions (23%). Grade 3 AEs seen in 1 patient each included colitis, maculopapular rash, asymptomatic elevated amylase/lipase, and leukocytosis. The only grade 4 AE observed in 1 patient was myositis.

At a median follow-up time of 16.3 months (95% CI, 6.9–not applicable [NA]), the median PFS was 7.4 months (95% CI, 5.6-NA) and the median OS was 15.1 months (95% CI, 7.7-NA). Additionally, the median duration of response for patients treated with the combination was 7.7 months (95% CI, 3.8-NA). Treatment with encorafenib and cetuximab alone yielded a median PFS of 4.2 months (95% CI, 3.7-5.4) and a median OS of 9.3 months (95% CI, 8.0-11.3).

“For patients who are experiencing responses, there is continued reduction in tumor size across the period of treatment,” Morris explained in his presentation. “For the 11 patients who continue to remain on study, 2 of the patients remain on treatment with encorafenib, cetuximab, and nivolumab at 100 weeks.”


Morris VK, Parseghian CM, Escano M, et al. Phase I/II trial of encorafenib, cetuximab, and nivolumab in patients with microsatellite stable, BRAFV600E metastatic colorectal cancer. Presented at: 2022 Gastrointestinal Cancers Symposium; January 20-22, 2022; Virtual. Abstract 12.

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