Skip to main content
Premium Trial:

Request an Annual Quote

C4 Therapeutics Begins Phase I/II Trial of Protein Degrader in BRAF V600-Mutant Solid Tumors

NEW YORK – C4 Therapeutics on Monday said it began studying its protein degrader CFT1946 in a Phase I/II trial involving patients with BRAF V600-mutant solid tumors.

In one arm of the Phase I trial, investigators will study CFT1946 as a single agent in patients with BRAF V600-mutant solid tumors. Later, the company will open another arm to explore CFT1946 with Novartis' MEK inhibitor Mekinist (trametinib), also in patients with BRAF V600-mutated solid tumors.

Once a recommended dose is established, the trial will expand into Phase II with three arms. One arm will explore the activity of CFT1946 monotherapy in patients with BRAF V600-mutant melanoma or non-small cell lung cancer who have received prior BRAF-targeted treatment. A second arm will assess CFT1946 with Mekinist in the same setting and a third arm will test CFT1946 with Mekinist in patients with BRAF V600-mutant NSCLC who have not received a BRAF inhibitor. C4 is tracking CFT1946's safety, tolerability, and anti-tumor activity in this trial.

The Watertown, Massachusetts-based company developed CFT1946 as a bifunctional degradation-activating compound (BiDAC). One of the molecule's functional groups binds the target BRAF V600-mutant protein and another binds E3 ubiquitin ligase, which initiates ubiquitination, the first step leading to destruction of the protein by the proteasome.

In vitro, CFT1946 led to BRAF V600E degradation, inhibited MAPK signaling, and killed BRAF V600E-mutant cells, but not wild-type BRAF cells. In mice with BRAF V600E mutations, meanwhile, CFT1946 induced tumor regression, and the drug was also active in models where cancers were resistant to BRAF inhibitors.

C4 has two other clinical phase cancer drug programs. CFT8634 targets BRD9 and is in Phase I development for cancers that depend on BRD9, including synovial sarcoma and SMARCB1-null cancers. The firm's other program, CFT7455, targets IKZF1/3. That Phase I/II trial involves patients with relapsed or refractory multiple myeloma and non-Hodgkin lymphoma.