BRAF mutation

P1/2, N=162, Recruiting, Association Gercor | Not yet recruiting --> Recruiting

P2, N=60, Not yet recruiting, Gustave Roussy, Cancer Campus, Grand Paris

Patients with metastatic colorectal cancer (mCRC) who have progressed on fluoropyrimidines, oxaliplatin, irinotecan, anti-angiogenic agents, and anti-epidermal growth factor receptor (EGFR) therapies have limited treatment options and poor prognosis, with a median overall survival (mOS) of ∼6 months on single-agent regorafenib or trifluridine/tipiracil. Tumor assessments occur every 8 weeks; follow-up continues for up to 18 months after enrolment. Optional translational research includes tumor, blood, and stool sampling to explore biomarkers of response and resistance.

Conclusions Lenvatinib showed substantial efficacy in BRAF-mutated PTC, while TERT mutations did not predict poor outcomes. The identification of five genes associated with early treatment failure highlights the potential for genomic biomarkers to guide personalized therapy.

P2, N=65, Not yet recruiting, Rapa Therapeutics LLC | Trial completion date: Sep 2028 --> Sep 2029 | Trial primary completion date: Mar 2028 --> Mar 2029

P=N/A, N=40, Enrolling by invitation, Chang Gung Memorial Hospital | Not yet recruiting --> Enrolling by invitation

Functional studies reveal that AR-driven autophagy confers resistance to BRAFi by enhancing cellular survival under therapeutic stress. Our findings establish AR-regulated autophagy as a critical resistance mechanism and provide preclinical evidence for combining AR-targeting PROTAC degrader ARV110 with autophagy inhibitors to overcome BRAFi resistance.

P2, N=161, Completed, Seagen, a wholly owned subsidiary of Pfizer | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Feb 2026 | Trial primary completion date: Dec 2026 --> Feb 2026

Solid organoids were more trametinib-sensitive and exhibited higher Wnt-3a levels, suggesting divergent cell compositions and pathway dependencies. Our findings highlight the functional relevance of non-genetic variability in organoid cultures and establish a framework to improve reproducibility and biological insight in PDO-based drug screening.

These molecular tools have the potential to change how CRC is managed by earlier detection and more precise predictive biomarkers. However, large-scale validation and clinical standardization are still crucial for their extensive utilization.