C4 Therapeutics has dosed the first subject in Phase I/II clinical trial of its CFT8634 to treat SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumours.
An orally bioavailable BiDAC degrader acting on BRD9, CFT8634 is intended to treat cancers that are dependent on BRD9.
BRD9 was deemed to be an ‘undruggable’ target because of bromodomain inhibitors’ inability to efficiently treat such cancers.
As opposed to BRD9 inhibition, BRD9 degradation was demonstrated to be efficacious in pre-clinical models of synovial sarcoma.
The trial will analyse the safety, tolerability and anti-tumour activity of CFT8634 for treating SMARCB1-perturbed cancers.
Characterising the pharmacokinetic and pharmacodynamic profile of the therapy are the secondary and exploratory objectives of the trial.
The Phase I segment will assess CFT8634 as an oral, single-agent treatment in patients with synovial sarcoma and SMARCB1-null tumours to detect a recommended Phase II dose.
On identifying the recommended dose, the Phase II segment will be extended to investigational arms in synovial sarcoma and SMARCB1-null tumours, respectively.
The company intends to enrol nearly 90 subjects in Phase I/II trial.
C4 Therapeutics chief medical officer Adam Crystal said: “The initiation of our first clinical trial of CFT8634 is a significant milestone for C4 Therapeutics as we apply our TORPEDO platform to an oncology target currently considered ‘undruggable’ and work to provide a new treatment option for patients living with synovial sarcoma and SMARCB1-null tumours.
“Based on our pre-clinical research showing that the BRD9 degrader CFT8634 is potent, selective and efficacious in models of synovial sarcoma and malignant rhabdoid tumours, we believe CFT8634 may offer an effective targeted treatment for patients who currently have limited therapeutic options.”
CFT8634 is the second oncology programme from the company’s in-house developed research pipeline to enter clinics.
Synovial sarcoma is a rare and aggressive soft tissue sarcoma subtype while SMARCB1-null tumours comprise malignant rhabdoid tumour, epithelioid sarcoma, poorly differentiated chordoma and various rare cancers.