Study of HLD-0915 in Patients With Metastatic Prostate Cancer

This is a Phase 1/2 study of the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of oral single-agent HLD-0915.

The study includes an initial Phase 1 open-label portion to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) of HLD-0915 as monotherapy, followed by Phase 2 expansion cohorts to further evaluate the safety and efficacy of HLD-0915.

Phase 1 is conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior systemic therapies. Phase 1 includes Part 1, an open-label monotherapy dose-escalation using a Bayesian optimal interval with backfill (BF-BOIN) design. Phase 1 also includes Part 2 (open-label), which evaluates the relative bioavailability of HLD-0915 formulations.

Phase 2 will evaluate the safety, PK, and anti-tumor activity of HLD-0915 administered at the RDEs. Phase 2, Part 1 will randomize patients and assess dose strengths in patients with mCRPC to support registrational dose selection. Additional Phase 2 open-label expansion cohorts will further evaluate preliminary safety and efficacy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Patients must meet the following criteria to be eligible study participation:

Key Inclusion Criteria:

All Study Arms (Phase 1 Part 1 & 2, Phase 2 Part 1, Part 2A, 2B, 2C & 2D):

Males ≥ 18 years old Histological, pathological, and/or cytological confirmation of prostate adenocarcinoma Adequate hematological, renal, and hepatic function. Able to swallow oral medication

mCRPC Arms: (Phase 1 Part 1 & 2, Phase 2 Part 1): Prior orchiectomy or ongoing androgen-deprivation therapy and a castrate level of serum testosterone Progressive mCRPC defined as having demonstrated PSA progression on the prior regimen

SOAR Arm (Phase 2 Part 2A) mHSPC with distant metastatic disease based on conventional imaging PSA ≥0.2 ng/mL, following treatment with next generation ARPI for at least 180 days and up to 365 days No evidence of radiographic or PSA progression while receiving ARPI

mHSPC arms (Phase 2 Part 2B, 2C & 2D) serum testosterone >150ng/ml mHSPC with distant metastatic disease based on conventional imaging and PSA >2.0 ng/mL

Key Exclusion Criteria:

All arms (Phase 1 Part 1 & 2, Phase 2 Part 1, Part 2A, 2B, 2C & 2D):

Has experienced a recent major bleed or has a known bleeding disorder Tumors exhibiting neuroendocrine or small cell carcinoma component by histopathology Receiving continuous corticosteroids at prednisone-equivalent dose of >10 mg/day Prior or ongoing significant medical condition

mCRPC arms: (Phase 1 Part 1 & 2, Phase 2 Part 1): Has received systemic anti-cancer therapy or investigational drugs within 2 weeks prior to first dose of study drug with certain exceptions requiring longer washout periods

SOAR arm (Phase 2 Part 2A) Has received any prior cytotoxic chemotherapy for prostate cancer

mHSPC arms (Phase 2 Part 2B, 2C & 2D) regional pelvic lymph node disease only