CFT1946

As CFT1946 progresses through clinical development, the field of oncoprotein-specific degradation will mature. See related article by Kreger et al., p. 438.

P1, N=89, Completed, C4 Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Apr 2027 --> Nov 2025 | Trial primary completion date: Mar 2027 --> Nov 2025

CFT1946 was efficacious in an intracranial BRAFV600E melanoma tumor model and demonstrated robust activity in multiple cellular and patient-derived BRAFV600-mutant melanoma and CRC models of acquired and adaptive RAF-dimer driven BRAFi-resistance. CFT1946 therefore represents an effective therapeutic modality with the potential to overcome the key limitations of current BRAFV600-mutant targeted therapies.

P1, N=89, Active, not recruiting, C4 Therapeutics, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1/2 --> P1 | N=206 --> 89

P1/2, N=206, Recruiting, C4 Therapeutics, Inc. | N=102 --> 206

The study is anticipated to enroll 101-122 patients across 11 participating US and European sites and is currently open to enrollment (NCT05668585). Clinical trial information: NCT05668585.

P1/2, N=122, Recruiting, C4 Therapeutics, Inc.

BRAF inhibitors including vemurafenib, dabrafenib and encorafenib have produced impressive responses in V600X patients, however resistance usually emerges within a year, including RAS mutation, BRAFV600E amplification, and BRAFV600E intragenic deletion or splice variants...The combination of encorafenib and trametinib showed no activity in the same model...Based on its activity in preclinical models, including models of BRAF inhibitor resistance, and its drug-like properties we are progressing CFT1946 as a candidate for clinical development in patients with solid tumors bearing BRAF V600X mutations. Further, given CFT1946’s activity on non-V600 BRAF mutations, we are continuing to explore CFT1946 and related BiDAC degraders as therapeutic options for patients bearing Class II or Class III BRAF mutations.