Study of HLD-0915 in Patients With Metastatic Prostate Cancer

Purpose

Assessment of the safety and efficacy of HLD-0915 in patients with metastatic prostate cancer who have progressed on prior systemic therapies, with further evaluation in additional prostate cancer populations.

Condition

  • Metastatic Prostate Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
Male
Accepts Healthy Volunteers
No

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

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
This multi-phase, multi-part study evaluates safety, PK, and preliminary efficacy of HLD-0915 across mPC disease states, while supporting dose selection and formulation development. Phase 1: Part 1 (Dose Escalation) uses a BF-BOIN design to identify the MTD and RDE. This adaptive approach allows enrollment at doses already shown to be safe, generating additional safety, tolerability, and early activity data to inform dose selection. Part 2 (Formulation Exploration) evaluates the relative bioavailability of new HLD-0915 formulations at doses demonstrated to be safe. Phase 2: Part 1 (Dose Optimization) evaluates anti-tumor activity at different randomized RDE(s) while continuing to assess safety and PK. Part 2 (Parts 2A,2B,2C,2D) Expansion Cohorts assesses safety and early efficacy at the RDE (or highest dose deemed safe) in defined metastatic HSPC populations. The design aims to establish dose and formulation and to characterize therapeutic potential across mPC populations.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
HLD-0915 Phase 1 Part 1 - Dose Escalation 		Treatment cycle consists of 21 days. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.)
  • Drug: HLD-0915 Hard Capsule
    Experimental: Oral HLD-0915
Experimental
HLD-0915 Phase 1 Part 2 - Formulation Exploration 		Hard capsule: Single 50mg dose Tablet: Single 50mg dose, followed by daily dosing through Cycle 2. Soft capsule: 50mg daily in 21-day treatment cycles. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.)
  • Drug: HLD-0915 Hard Capsule
    Experimental: Oral HLD-0915
  • Drug: HLD-0915 Tablet
    Experimental: Oral HLD-0915
  • Drug: HLD-0915 Soft Capsule
    Experimental: Oral HLD-0915
Experimental
HLD-0915 Phase 2 Part 1 - Dose Optimization 		Hard Capsules 25mg or 50 mg Treatment cycle consists of 21 days. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.)
  • Drug: HLD-0915 Hard Capsule
    Experimental: Oral HLD-0915
Experimental
Phase 2 Part 2A - SOAR 		Hard Capsules Treatment cycle consists of 21 days. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.)
  • Drug: HLD-0915 Hard Capsule
    Experimental: Oral HLD-0915
Experimental
Phase 2 Part 2B - HSPC Expansion 		Hard Capsules Treatment cycle consists of 21 days. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.)
  • Drug: HLD-0915 Hard Capsule
    Experimental: Oral HLD-0915
Experimental
Phase 2 Part 2C - HSPC Expansion 		Hard capsules Treatment cycle consists of 21 days. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.)
  • Drug: HLD-0915 Hard Capsule
    Experimental: Oral HLD-0915
Experimental
Phase 2 Part 2D - HSPC Expansion 		HLD-0915 Hard Capsules Treatment cycle consists of 21 days. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.)
  • Drug: HLD-0915 Hard Capsule
    Experimental: Oral HLD-0915

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Halda Therapeutics OpCo, Inc.

Study Contact

Study Information
844-434-4210
Participate-In-This-Study1@its.jnj.com

Detailed Description

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).