Open-Label Study of Pocenbrodib Alone and in Combination With Abiraterone Acetate, Olaparib, or 177Lu-PSMA-617

This is a Phase 1b/2a multicenter, open-label study to confirm the safety,

pharmacokinetics (PK), preliminary antitumor activity, and pharmacodynamics (PD) of

pocenbrodib for the treatment of participants with mCRPC who have progressed despite

prior therapy and have been treated with at least 1 potent anti-androgen therapy

(enzalutamide, apalutamide, abiraterone acetate, or darolutamide).

The Phase 1b portion of the study involves pocenbrodib monotherapy at multiple,

sequential five rising doses (50, 100, 150, 200, and 250mg) initially using a QD dosing

schedule of 5 days on/2 days off. The first dose level (50 mg) will enroll at least 3

participants (with 3 more added if the first 3 participants yield 1 dose-limiting

toxicity). Once safety is confirmed through Data Review Committee (DRC), the next higher

pocenbrodib dose level cohort can begin enrollment.

If both acceptable safety and minimal threshold of efficacy (predefined as 30% PSA50 are

achieved, the sponsor will proceed to Phase 2a.

Phase 2a will enroll participants in each of 4 cohorts: pocenbrodib monotherapy (2A), and

3 combination therapy cohorts: pocenbrodib + abiraterone acetate (2B), pocenbrodib +

olaparib (2C), and pocenbrodib + 177Lu-PSMA-617 (2D). All cohorts may enroll in parallel,

but each cohort will be evaluated independently for safety and efficacy.