C4 Therapeutics, Inc. (C4T) announced that the first patient has been dosed in its Phase 1/2 clinical trial of CFT8634, an orally bioavailable BiDAC™ degrader targeting BRD9 for the treatment of SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors. The Phase 1/2 trial will primarily investigate safety, tolerability and anti-tumor activity with secondary and exploratory objectives to characterize the pharmacokinetic and pharmacodynamic profile of CFT8634. The Phase 1 portion of the study will evaluate CFT8634 as an oral, single agent therapy for patients with synovial sarcoma and SMARCB1-null tumors to identify a recommended Phase 2 dose.

Following identification of recommended dosage, the Phase 2 portion of the trial is expected to expand to the following investigational arms: one in synovial sarcoma, and one in SMARCB1-null tumors. Across the Phase 1/2 trial, C4T plans to enroll approximately 90 patients. CFT8634 is C4T's second oncology program to enter clinical studies from its internally developed research pipeline.

CFT8634 is C4T's first BiDAC degrader candidate to be evaluated in the clinic. CFT8634 is a BiDAC™ degrader targeting BRD9 for the treatment of cancers that are dependent on BRD9, including synovial sarcoma and SMARCB1-null cancers. BRD9 has been considered an “undruggable” target due to the inability of bromodomain inhibitors to effectively treat these cancers.

Unlike BRD9 inhibition, BRD9 degradation has been shown to be efficacious in pre-clinical models of synovial sarcoma. By leveraging C4T's TORPEDO® platform, C4T developed CFT8634, an orally bioavailable, selective degrader of BRD9. In March 2022, C4T announced the U.S. Food and Drug Administration had granted orphan drug designation (ODD) to CFT8634.

Synovial sarcoma is a rare and aggressive subtype of soft tissue sarcoma. It accounts for approximately 10% of all sarcoma diagnoses. An estimated 900 people are diagnosed with synovial sarcoma in the U.S. each year.

Approximately one-third of patients are diagnosed under the age of 30. SMARCB1-null tumors include malignant rhabdoid tumor, poorly differentiated chordoma, epithelioid sarcoma and other rare cancers; some subtypes are most commonly diagnosed in children and young adults. Both synovial sarcoma and SMARCB1-null tumors are believed to be dependent on BRD9 and, as a result, CFT8634 may be an effective treatment.