Phase 1/2 Study of HLD-0915 (JNJ-101556143) in Patients With Metastatic Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 190
- 试验地点
- 18
- 主要终点
- Frequency of dose-limiting toxicities (DLTs)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.)
干预措施: 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.)
干预措施: 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.)
干预措施: 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.)
干预措施: 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.)
干预措施: 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.)
干预措施: 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.)
干预措施: 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.)
干预措施: 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.)
干预措施: JNJ-101556143 Formulation 3 (Drug)
结局指标
主要结局
Frequency of dose-limiting toxicities (DLTs)
时间窗: 21 days
Frequency and severity of AEs and abnormal ECG, laboratory and clinical changes since baseline
时间窗: 21 days
Phase 1 Part 2 (formulation exploration) relative bioavailability
时间窗: 22 days
次要结局
- 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)