Overview
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.
Description
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
Key Inclusion Criteria:
All patients must meet the following criteria to be eligible for Phase 1 study participation:
- Males of age 18 years at the time of signing the informed consent form (ICF).
- Able to understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures.
- Patients must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
- Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone.
- Patients must have progressed on prior line(s) of therapy.
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Life expectancy of at least 3 months.
- Adequate hematological, renal, and hepatic function.
- Able to swallow an oral medication.
- Willing and able to adhere to the study visit schedule and other protocol requirements.
- 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:
- 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.
- 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.
- History of myocardial infarction or unstable angina within 6 months prior to enrollment, or clinically significant cardiac disease.
- Known clinically significant active or chronic infection.
- Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease.