Phase 1b/2 Safety and Efficacy Study of NUV-422 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 3
- 主要终点
- Phase 2 Dose Expansion: Objective response rate (ORR)
研究概览
简要总结
NUV-422-04 is an open-label Phase 1b/2 dose escalation and expansion study designed to evaluate the safety and efficacy of NUV-422 in combination with enzalutamide. The study population is comprised of adults with mCRPC. Patients will self-administer NUV-422 and 160 mg enzalutamide orally in 28-day cycles. Patients will be treated until disease progression, toxicity, withdrawal of consent, or termination of the study.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of metastatic castration-resistant prostate cancer with disease progression despite castrate levels of testosterone
- •Have radiographic or biochemical evidence of progression as determined by Investigator per standard criteria
- •Have no known active or symptomatic central nervous system (CNS) disease
- •Prior therapy with abiraterone required and:
- •For Phase 1b only: up to 2 prior taxane-based chemotherapy regimens allowed for castration-resistant disease
- •For Phase 2 only: Patients must not have received prior taxane-based chemotherapy for castrate-resistant disease or prior treatment with CDK inhibitors
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2
- •Adequate bone marrow and organ function
- •Eligible to receive enzalutamide
- •Life expectancy of > 6 months
排除标准
- •History of seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma)
- •Have received chemotherapy, hormonal therapy (with the exception of ongoing LHRH analogs) radiation, or biological anti-cancer therapy within 14 days prior to first dose of NUV-422 and enzalutamide
- •Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent or 21 days (or < 5 half-lives) for myelosuppressive agent prior to the first dose of NUV-422 and enzalutamide
- •Requires medications that are known to be strong inducers and /or inhibitors of CYP3A4/5 enzymes, except enzalutamide
- •For Phase 1b only: Requires medications that are known to be moderate inducers and /or inhibitors of CYP3A4/5 enzymes, except enzalutamide
- •Prior therapy with enzalutamide, apalutamide, darolutamide, or investigational androgen receptor inhibitors
- •Known allergy or hypersensitivity to enzalutamide
研究组 & 干预措施
Phase 1b Dose Escalation
NUV-422 will be administered orally at escalating dose levels in combination with enzalutamide until the recommended Phase 2 combination dose (RP2cD) is determined.
160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-422.
干预措施: NUV-422 (Drug)
Phase 1b Dose Escalation
NUV-422 will be administered orally at escalating dose levels in combination with enzalutamide until the recommended Phase 2 combination dose (RP2cD) is determined.
160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-422.
干预措施: Enzalutamide (Drug)
Phase 2
NUV-422 will be administered orally at the RP2cD in combination with enzalutamide.
160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-422.
干预措施: NUV-422 (Drug)
Phase 2
NUV-422 will be administered orally at the RP2cD in combination with enzalutamide.
160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-422.
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Phase 2 Dose Expansion: Objective response rate (ORR)
时间窗: Every 8 weeks throughout study treatment, an average of 6 months
ORR per standard criteria
Phase 1b Dose Escalation: Safety and tolerability of NUV-422 in combination with enzalutamide to determine the recommended Phase 2 combination dose (RP2cD)
时间窗: During the DLT period (28 days)
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and laboratory abnormalities
Phase 2 Dose Expansion: Prostate-specific antigen (PSA)-response rate (PSA-RR)
时间窗: Every 4 weeks throughout study treatment, an average of 6 months
PSA per standard criteria
次要结局
未报告次要终点