C4 Therapeutics Presents Monotherapy Data Demonstrating Proof of Mechanism and Early Evidence of Proof of Concept From Ongoing CFT1946 Phase 1 Trial in BRAF V600 Mutant Solid Tumors at the European Society for Medical Oncology (ESMO) Congress 2024

Core Insights - CFT1946 is the first and only clinical-stage degrader targeting BRAF V600 mutations, showing promise in disrupting the current treatment landscape for patients with solid tumors [2][10] - Initial clinical data indicate that CFT1946 has a well-tolerated safety profile, dose-dependent pharmacokinetics, and early evidence of anti-tumor activity [3][5][10] - The ongoing Phase 1 trial is expected to provide additional data in 2025, with multiple indication-specific cohorts advancing [7] Safety and Tolerability - CFT1946 has demonstrated a well-tolerated safety profile with no dose-limiting toxicities or treatment-related serious adverse events [3][4] - Adverse events were primarily Grade 1 or Grade 2, with no patients discontinuing therapy due to treatment-related adverse events [4] Pharmacokinetics and Pharmacodynamics - Initial data show dose-dependent bioavailability and effective degradation of BRAF V600E protein, supporting the proof of mechanism for CFT1946 [5][10] - All available post-treatment biopsies indicated successful degradation of the target protein [5] Anti-Tumor Activity - Among 27 evaluable patients, 16 showed a reduction in target metastatic lesions, with two achieving confirmed Partial Response [6] - Notable reductions were observed across various tumor types, including a 67% decrease in a patient with Stage IV BRAF V600K melanoma and a 55% decrease in a patient with Stage IV BRAF V600E pancreatic cancer [6] Future Milestones - The Phase 1 trial will continue with a focus on completing monotherapy dose escalation and exploring combination therapies with cetuximab and trametinib [7] - Full monotherapy dose escalation data and expansion cohort results are anticipated in 2025 [7]