624P - Tolerability and safety of vemurafenib, cetuximab combined with camrelizumab for BRAF V600E-mutated /MSS metastatic colorectal cancer

Background

The doublet combination of the BRAF inhibitor and the EGFR antibody showed unsatisfactory effect for patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC). Furthermore, multiple immune escape mechanisms exist in BARF V600E mutated/MSS tumors. Combining targeted therapy with PD-1 antibody is a promising treatment option.

Methods

We enrolled previously treated patients with BRAF V600E-mutated/MSS mCRC. Eligible patients had received at least one systemic treatment for metastatic disease, not include EGFR inhibitor, BRAF inhibitor, and PD-1 inhibitor (ECOG PS 0-1) and had at least one measurable disease according to RECIST 1.1. All enrolled patients received cetuximab (500mg/m2, iv, q14 days), camrelizumab (200mg, iv, q14 days) and vemurafenib (two dose levels of 960mg, po, daily or twice daily). The primary endpoints were safety, tolerability per CTCAE.5 The second endpoints included ORR, DCR, PFS per RECIST1.1 and OS.

Results

12 patients were enrolled and received trial regimen. Median age is 51 years, and 50% were male. Because of the high incidence of AEs in first 3 patients, all patients finally treated with lower dose of vemurafenib (960mg, po, daily). With a median follow-up of 13.68 months, grade 1-2 treatment-related AEs occurred in 12 patients (100.0%). Grade 1-2 AEs included drug-related rash (75.0%), articular pain (75.0%), reactive capillary proliferation disease (66.7%), anemia (53.3%), muscular pain (41.7%), mucosal hemorrhage (41.7%), fatigue (25.0%), and mouth ulcers (16.7%).6 patients (50.0%) had grade 3 treatment-related AEs, included fever (25%), drug-related rash (16.7%), mucosal hemorrhage (8.3%), diarrhea (8.3%), immune myocarditis (8.3%), anemia (8.3%), thrombocytopenia (8.3%), mucosal hemorrhage (8.3%), and immunological myocarditis (8.3%). Finally, 10 patients received response evaluation. ORR is 40.0%, and DCR is 80.0%. 1 patient achieved CR with duration of response of 24.83 months. 3 patients achieved PR and 4 patients were evaluated as SD. Median PFS is 3.37 months (95%CI, 1.28-5.26). Median OS is 11.47 months (95%CI, 4.67-18.27).

Conclusions

The VCC regimen is effective and moderate-tolerated for patients with BRAF V600E-mutated /MSS mCRC.

Clinical trial identification

NCT05019534.

Editorial acknowledgement

None

Legal entity responsible for the study

West China Hospital.

Funding

1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC21017) and 2021 CSWOG Oncology Innovative Combination Clinical Research Grant.

Disclosure

All authors have declared no conflicts of interest.