Combination Therapy for BRAF-V600E Metastatic CRCm

Progression-Free Survival (PFS)

The BRAVE is a phase II clinical trial aimed at evaluating the efficacy of the combination
 therapy of encorafenib, cetuximab, and bevacizumab in patients with metastatic colorectal
 cancer (CRC) harboring the BRAF-V600E mutation. This mutation is present in about 8-10% of
 CRC cases and is associated with poor prognosis and limited treatment options. The rationale
 behind this trial stems from preclinical studies suggesting that the overexpression and
 activation of vascular endothelial growth factor A (VEGFA) may contribute to resistance to
 BRAF inhibitors (BRAFi) in CRC. Thus, the trial hypothesizes that adding bevacizumab, an
 anti-angiogenic agent targeting VEGFA, to the combination of encorafenib and cetuximab may
 delay acquired resistance, leading to improved progression-free survival.
 
 The primary objective of the BRAVE is to evaluate the antitumor activity of the
 encorafenib-cetuximab-bevacizumab combination in patients who have experienced disease
 progression after one or two chemotherapy regimens for BRAF V600E-mutant metastatic CRC. This
 activity will be assessed based on the confirmed progression-free survival rate according to
 Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.