Study of Resistance Mechanisms to BRAF and EGFR Targeted Treatment in Adults with BRAF V600E-mutated Metastatic Colorectal Cancer Using Standard Combination Therapy with Encorafenib, Cetuximab, and Chemotherapy

What this Trial Is About

Researchers are studying primary and acquired resistance mechanisms to standard treatments targeting BRAF V600E mutations in metastatic colorectal cancer. This observational study focuses on patients receiving combined therapy with BRAF inhibitor encorafenib, anti-EGFR antibody cetuximab, and chemotherapy. Resistance to this combination often develops, limiting treatment options, so the study aims to uncover genetic and non-genetic reasons behind this resistance to help develop better future therapies. Participants will receive standard-of-care treatment with encorafenib, cetuximab, and possibly chemotherapy. Before starting treatment and at the time of disease progression, researchers will collect tumor tissue, blood, and stool samples. These samples will be used to study molecular changes and the microbiome, and to create patient-derived organoids for laboratory testing. Blood samples will be collected regularly during treatment to analyze circulating tumor DNA over time. Throughout the study, participants will be followed longitudinally with sample collections before treatment and at progression, continuing for up to around 24 months. Researchers will measure molecular alterations linked to resistance, compare tissue and liquid biopsy findings, characterize gut microbiome changes, and track tumor DNA dynamics. The studys findings aim to improve understanding of resistance and support personalized treatment approaches for metastatic colorectal cancer.

Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer