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

[INTRODUCTION] 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.

[METHODS] 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/m; camrelizumab 200 mg; vemurafenib 960 mg orally once daily). Adverse events and efficacy were monitored and recorded throughout the administration and follow-up period.

[RESULTS] 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.

[CONCLUSIONS] 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).