PATHWAY: A Phase 1b/2a, Multicenter, Open- Label Study of Pocenbrodib as Monotherapy and in Combination With Darolutamide in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 25
- 主要终点
- Dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D)
研究概览
简要总结
This is a dose-finding study to assess the safety and preliminary antitumor activity of Pocenbrodib alone or with darolutamide in patients with metastatic castration-resistant prostate cancer (mCRPC)
详细描述
This is a Phase 1b/2a multicenter, open-label study to confirm the safety, pharmacokinetics (PK), preliminary antitumor activity, and pharmacodynamics (PD) of pocenbrodib for the treatment of participants with mCRPC who have progressed following prior therapy and have been treated with at least 1 potent anti-androgen therapy (enzalutamide, apalutamide, abiraterone acetate, or darolutamide).
Phase 1b is a dose escalation and optimization study of pocenbrodib monotherapy and in combination with darolutamide in order to determine the maximum tolerated dose (MTD) in participants (n=80) and to determine the recommended Phase 2 dose(s) (RP2D(s)).
Phase 1b consists of three arms: Arm 1 (50-250mg QD 5/2), Arm 2 (continuous monotherapy, 125mg-150mg BID), and Arm 3 (continuous combination of pocenbrodib 125-150mg BID + darolutamide 600mg BID), with DRC safety gates governing study progression between arms. Arm 3 is considered the safety run-in for the combination therapy.
Phase 2a is a dose expansion portion of the study to further evaluate the combination of pocenbrodib and darolutamide in participants with mCRPC who have progressed following lutetium-Lu-177-vipivotide-tetraxetan (PLUVICTO) and prior to initiation of taxane-based therapy and will consist of 2 cohorts:
Cohort 1: pocenbrodib RP2D high + darolutamide
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
- •1b / 2a Inclusion Criteria:
- •≥18 years of age
- •Histologic documentation of prostate adenocarcinoma
- •Metastatic disease, documented by imaging. Imaging performed within 56 days prior to Screening is acceptable
排除标准
- •Current or prior evidence of any small cell or neuroendocrine histology on the most recent prostate biopsy.
- •Any liver metastases confirmed by biopsy or evidence of lesions >1 cm consistent with liver metastases on imaging.
- •Intervention with any chemotherapy, investigational agent, or other anticancer drug, including enzalutamide, apalutamide, or darolutamide, 14 days prior to Cycle 1 Day 1 or 5 half-lives (whichever is shorter).
- •Any other serious underlying medical, psychiatric, psychological, familial, or geographical condition, which in the judgment of the Investigator may interfere with study participation and compliance or place the participant at high risk from treatment-related complications.
- •2a only -key inclusion criteria:
- •Must have received at least 2 cycles of PLUVICTO®
- •1 line of prior any ARPI therapy
- •No prior chemotherapy for mCRPC
研究组 & 干预措施
Phase 1b Arm 3
Pocenbrodib 125-150 mg BID + darolutamide 600 mg
干预措施: Pocenbrodib and Darolutamide (Drug)
Phase 2a portion
Cohort 1: pocenbrodib RP2D-high + darolutamide Cohort 2: pocenbrodib RP2D-low + darolutamide
干预措施: Pocenbrodib and Darolutamide (Drug)
Phase 1b Arm 1
Pocenbrodib 50-250 mg QD (5 days on/2 days off)
干预措施: Pocenbrodib (Drug)
Phase 1b Arm 2
Pocenbrodib 125-150 mg BID monotherapy
干预措施: Pocenbrodib (Drug)
结局指标
主要结局
Dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D)
时间窗: 28-day
DLT, serious adverse events (SAEs), clinically relevant adverse events (AEs), and clinically relevant safety laboratory values
RECIST v1.1 objective response rate (ORR)
时间窗: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
Proportion of participants with ORR. The response rate will be reported with an exact 95% CI.
Prostate specific antigen (PSA)
时间窗: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
PSA decline post-treatment = ≥ 30% PSA50. The PSA will be reported with an exact 95% CI.
次要结局
- Maximum Plasma Concentration Observed (Cmax)(At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first)
- PSA30(From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.)
- PSA50(From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.)
- PSA90(From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.)
- Progression Free Survival (PFS)(From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.)
- Time to Progression (TTP)(From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.)
- Time of Maximum Plasma Concentration Observed (Tmax)(At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first)
- Overall Survival (OS)(From date of first study drug dose until the date of date of death from any cause assessed up to approximately 32 months)
- Terminal Half-Life (T1/2)(At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first)