Randomized, Non-Comparative Phase 1/2 Study of NUV-422 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative (HR+HER2-) Advanced Breast Cancer (aBC)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 5
- 主要终点
- Phase 1b Dose Escalation: Safety and tolerability of NUV-422 in combination with fulvestrant to determine the recommended Phase 2 combination dose (RP2cD)
研究概览
简要总结
NUV-422-03 is a randomized, non-comparative Phase 1/2 dose escalation and expansion study designed to evaluate the safety and efficacy of NUV-422 in combination with fulvestrant relative to NUV-422 monotherapy and fulvestrant monotherapy. The study population is comprised of adults with HR+HER2- aBC. Patients will self-administer NUV-422 orally in 28-day cycles and receive 500 mg fulvestrant intramuscularly (IM) on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter. 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
- 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
- •Men and women with diagnosis of locally advanced inoperable or metastatic HR+HER2- breast cancer
- •Evidence of disease progression on immediate prior therapy as determined by the Investigator per standard criteria
- •Patients must have received standard of care treatments for their breast cancer and be eligible to receive fulvestrant
- •Prior standard of care treatments must include treatment with hormonal therapy in combination with an approved CDK4/6 inhibitor
- •Patients must have endocrine-resistant disease
- •Have no known active or symptomatic central nervous system (CNS) disease
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1
- •Life expectancy of > 6 months
- •Eligible to receive fulvestrant
- •Adequate bone marrow and organ function
排除标准
- •Have received chemotherapy, hormonal therapy (with the exception of ongoing LHRH analogs in male patients and premenopausal women), radiation, or biological anti-cancer therapy within 14 days prior to the first dose of NUV-422 and fulvestrant
- •Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent or 21 days (of < 5 half-lives) for myelosuppressive agent prior to first dose of NUV-422 and fulvestrant
- •Moderate liver impairment which would require a reduced dose of fulvestrant
- •Requires medications that are known to be strong inducers and/or inhibitors of CYP3A4/5 enzymes
- •For Phase 1b only: requires medications that are known to be moderate inducers and/or inhibitors of CYP3A4/5 enzymes
- •Known allergy or hypersensitivity to fulvestrant
- •For Phase 2 only: prior therapy with fulvestrant and/or investigational ER targeted agent
- •Females who are pregnant or breast feeding
研究组 & 干预措施
Phase 1b Dose Escalation
NUV-422 will be administered orally at escalating dose levels in combination with fulvestrant until the recommended Phase 2 combination dose (RP2cD) is determined.
500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
干预措施: NUV-422 (Drug)
Phase 1b Dose Escalation
NUV-422 will be administered orally at escalating dose levels in combination with fulvestrant until the recommended Phase 2 combination dose (RP2cD) is determined.
500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
干预措施: Fulvestrant (Drug)
Phase 2 NUV-422 + fulvestrant
NUV-422 will be administered orally at the RP2cD in combination with fulvestrant.
500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
干预措施: NUV-422 (Drug)
Phase 2 NUV-422 + fulvestrant
NUV-422 will be administered orally at the RP2cD in combination with fulvestrant.
500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
干预措施: Fulvestrant (Drug)
Phase 2 NUV-422 monotherapy
NUV-422 will be administered orally at the RP2cD.
干预措施: NUV-422 (Drug)
Phase 2 fulvestrant monotherapy
500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Phase 1b Dose Escalation: Safety and tolerability of NUV-422 in combination with fulvestrant 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: Objective Response Rate (ORR)
时间窗: Every 8 weeks through study treatment, an average of 6 months
ORR per standard criteria
次要结局
未报告次要终点