A Study of HLD-0915 in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

Assessment of the safety and efficacy of HLD-0915 as monotherapy in patients with metastatic castration resistant prostate cancer (mCRPC) that have progressed on prior systemic therapies, once a recommended dose for expansion (RDE) has been determined in Phase 1 of the trial.

This is a Phase 1/2, open-label study of the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of oral single-agent HLD-0915. Patients on the study must continue androgen deprivation therapy (ADT) unless surgically castrated,

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

Phase 1 of this study is an open-label, dose-escalation and cohort expansion study in patients with mCRPC that have progressed after prior systemic therapies. Patients will be enrolled in monotherapy dose-escalation cohorts using a Bayesian optimal interval with backfill (BF-BOIN) design. Patients are treated in cohort size of 3 with the enrollment staggered between cohorts.

Phase 2 of this study will evaluate the anti-tumor activity of HLD-0915 administered at the RDEs in patients with mCRPC. Phase 2 study design and patient population will be based on the outcomes of Phase 1 of the trial.

Eligibility Criteria:
Key Inclusion Criteria:

All patients must meet the following criteria to be eligible for Phase 1 study participation:

1. Males of age 18 years at the time of signing the informed consent form (ICF).
2. Able to understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures.
3. Patients must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
4. Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone.
5. Patients must have progressed on prior line(s) of therapy.
6. Patients must have progressive mCRPC defined as having demonstrated PSA progression on the prior regimen. PSA progression may have occurred with or without accompanying radiographic progression.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8. Life expectancy of at least 3 months.
9. Adequate hematological, renal, and hepatic function.
10. Able to swallow an oral medication.
11. Willing and able to adhere to the study visit schedule and other protocol requirements.
12. Patients on a stable bisphosphonate or denosumab regimen for 30 days prior to enrollment are eligible.

Key Exclusion Criteria:

Patients with any of the following will be excluded from participation in Phase 1 of the study:

1. Has experienced a recent major bleed or has a known bleeding disorder.
2. Tumors exhibiting neuroendocrine or small cell carcinoma component by histopathology.
3. Receiving continuous corticosteroids at prednisone-equivalent dose of \>10 mg/day.
4. Has received systemic anti-cancer therapy (cytotoxic chemotherapy, biologic agent, checkpoint inhibitors, or radiation therapy) or investigational drugs within 2 weeks prior to first dose of study drug with certain exceptions requiring longer washout periods.
5. History of myocardial infarction or unstable angina within 6 months prior to enrollment, or clinically significant cardiac disease.
6. Known clinically significant active or chronic infection.
7. Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease.