Phase 1/2 Study of HLD-0915 (JNJ-101556143) in Patients With Metastatic Prostate Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 190
- Locations
- 18
- Primary Endpoint
- Frequency of dose-limiting toxicities (DLTs)
Study Overview
Brief Summary
Assessment of the safety and efficacy of HLD-0915 (JNJ-101556143) in patients with metastatic prostate cancer who have progressed on prior systemic therapies, with further evaluation in additional prostate cancer populations.
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).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
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
Arms & Interventions
JNJ-101556143 Phase 2 Part 1 - Dose Optimization
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.)
Intervention: JNJ-101556143 Formulation 1 (Drug)
JNJ-101556143 Phase 1 Part 2 - Formulation Exploration
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.)
Intervention: JNJ-101556143 Formulation 2 (Drug)
JNJ-101556143 Phase 1 Part 2 - Formulation Exploration
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.)
Intervention: JNJ-101556143 Formulation 1 (Drug)
Phase 2 Part 2A - SOAR
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.)
Intervention: JNJ-101556143 Formulation 1 (Drug)
Phase 2 Part 2B - HSPC Expansion
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.)
Intervention: JNJ-101556143 Formulation 1 (Drug)
Phase 2 Part 2C - HSPC Expansion
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.)
Intervention: JNJ-101556143 Formulation 1 (Drug)
Phase 2 Part 2D - HSPC Expansion
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.)
Intervention: JNJ-101556143 Formulation 1 (Drug)
JNJ-101556143 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.)
Intervention: JNJ-101556143 Formulation 1 (Drug)
JNJ-101556143 Phase 1 Part 2 - Formulation Exploration
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.)
Intervention: JNJ-101556143 Formulation 3 (Drug)
Outcomes
Primary Outcomes
Frequency of dose-limiting toxicities (DLTs)
Time Frame: 21 days
Frequency and severity of AEs and abnormal ECG, laboratory and clinical changes since baseline
Time Frame: 21 days
Phase 1 Part 2 (formulation exploration) relative bioavailability
Time Frame: 22 days
Secondary Outcomes
- PK Parameters(21 days)
- Change in PSA over time(21 days)
- Objective Response Rate (ORR)(63 days)
- Duration of Response (DOR)(21 days)
- Radiographic Progression-Free Survival (rPFS)(63 days)
- Time to Response (TTR)(63 days)