Oncternal Therapeutics, Inc. announced that the first patient has been dosed in the Phase 1/2 dose escalation/dose expansion study of ONCT-534, the company?s dual-action androgen receptor inhibitor. ONCT-534 is a dual-action androgen receptor inhibitor (DAARI) that interacts with both the N-terminal domain and the ligand-binding domain (LBD) of the androgen receptor (AR), inhibiting cell growth and inducing AR degradation. Preclinical studies have shown activity in prostate cancer models against both unmutated AR, and against multiple mutations, including AR amplification, mutations in the AR LBD, and splice variants with loss of the AR LBD.

Study ONCT-534-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and anti-tumor activity of ONCT-534 in patients with metastatic castration-resistant prostate cancer (mCRPC) who have relapsed or are refractory to approved androgen receptor signaling inhibitors (ARSIs) including enzalutamide, abiraterone, apalutamide and darolutamide. After the safety and tolerability of ONCT-534 have been assessed to select the recommended Phase 2 dose (RP2D) in Phase 1, Phase 2 will commence to further validate the dose and evaluate the safety and efficacy of ONCT-534.