# Vemurafenib, cetuximab and camrelizumab in BRAF V600E-mutated/MSS metastatic colorectal cancer

## TL;DR

A new treatment combining three drugs shows manageable side effects and some effectiveness in treating a rare and aggressive form of colorectal cancer.

## Contribution

A pilot phase I trial testing a novel combination therapy for BRAF V600E-mutated metastatic colorectal cancer.

## Key findings

- The VCC regimen showed median overall survival of 7.19 months and progression-free survival of 3.47 months.
- Adverse events were common but manageable, with 50% of patients experiencing grade 3 or higher events.
- One patient achieved complete response and three achieved partial response to the treatment.

## Abstract

Patients with BRAF V600E-mutated/microsatellite stable (MSS) metastatic colorectal cancer (mCRC) are associated with a poor prognosis. Backline treatment has minimal efficacy. Multi-target inhibitors of the RAS-RAF-MEK signaling pathway combined with PD-1 monoclonal antibody may be a promising strategy for BRAF V600E-mutated mCRC.

This prospective phase I trial enrolled patients to explore tolerability and safety of the VCC regimen in previously treated patients with BRAF V600E-mutated/MSS mCRC. Enrolled patients treated with VCC therapy every 2 weeks (cetuximab 500mg/m2; camrelizumab 200 mg; vemurafenib 960 mg orally once daily). Adverse events and efficacy were monitored and recorded throughout the administration and follow-up period.

This trial enrolled 12 eligible patients. Total 2 patients had DLT: one had grade 3 thrombocytopenia and immune myocarditis, another had grade 3 vaginal bleeding. Adverse events (AEs) of grade 3 or higher occurred in 50% of patients. Grade 3 AEs were mainly drug-related fever (25.0%), drug-related rash (16.7%). Median overall survival (OS) and PFS were 7.19 months and 3.47 months, respectively. The ORR and DCR were 33.3% and 66.7%. One patient achieved CR. three patients achieved PR. An abnormal CD4/CD8 ratio was associated with a higher risk of progression. Different efficacy of VCC regimen may be attributed to the difference in tumor immune environment.

A combination of vemurafenib, cetuximab combined with camrelizumab exhibited manageable adverse reactions and efficacy in BRAF V600E-mutated/MSS patients with metastatic colorectal cancer who progressed after standard treatment. This is a pilot study and a larger phase II trials is planned to validate the findings. (ClinicalTrials.gov ID: NCT05019534).

The online version contains supplementary material available at 10.1186/s12967-025-07312-6.