A Multicenter, Open-Label, Phase Ib/II Randomized Study of JSKN016 in Combination With D-0502 in Patients With Locally Advanced or Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a multicenter, open-label, Phase Ib/II randomized study designed to evaluate the safety, tolerability, dose-limiting toxicities (DLTs), and preliminary antitumor activity of JSKN016 in combination with the oral selective estrogen receptor degrader (SERD) D-0502 in patients with locally advanced or metastatic hormone receptor-positive (HR+), HER2-negative breast cancer who have previously progressed on CDK4/6 inhibitor-based endocrine therapy.
Approximately 60 patients will be randomized in a 1:1 ratio to receive JSKN016 administered intravenously every 2 weeks (Q2W) or every 3 weeks (Q3W), in combination with daily oral D-0502. Each dosing cohort will include a safety lead-in phase to assess DLTs prior to cohort expansion. Tumor response will be assessed according to RECIST v1.1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age ≥18 years
- •Histologically or cytologically confirmed locally advanced or metastatic HR-positive, HER2-negative breast cancer
- •HR-positive defined as ER and/or PR ≥1% by IHC
- •HER2-negative per ASCO/CAP guidelines
- •At least one measurable extracranial lesion per RECIST v1.1
- •ECOG performance status 0-1
- •Prior progression on CDK4/6 inhibitor plus endocrine therapy
- •Adequate organ and cardiac function
- •Postmenopausal women, or premenopausal women receiving ovarian function suppression
排除标准
- •Active or untreated CNS metastases
- •Prior treatment with ADCs containing topoisomerase I inhibitor payloads
- •Active interstitial lung disease or pneumonitis
- •Uncontrolled cardiovascular disease or active infection
- •Prior malignancy within 5 years (with specific exceptions)
- •Pregnancy or breastfeeding
研究组 & 干预措施
JSKN016 Q2W + D-0502
干预措施: JSKN016 Q2W (Drug)
JSKN016 Q2W + D-0502
干预措施: D-0502 (Drug)
JSKN016 Q3W + D-0502
干预措施: JSKN016 Q3W (Drug)
JSKN016 Q3W + D-0502
干预措施: D-0502 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: From first dose through the end of Cycle 1 (approximately 21 days)
Safety and tolerability (TEAEs, TRAEs, SAEs)
时间窗: From first dose until 30 days after the last dose of study treatment.
Objective Response Rate (ORR)
时间窗: From first dose through treatment discontinuation, assessed up to 12 months
次要结局
- Progression-Free Survival (PFS)(From first dose until the first documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months)
- Overall Survival (OS)(From first dose until death from any cause, assessed up to 36 months)
- Disease Control Rate (DCR)(From first dose through 24 weeks)
- Duration of Response (DoR)(From first documented objective response (CR or PR) until disease progression or death, whichever occurs first, assessed up to 24 months)
- Clinical Benefit Rate (CBR)(From first dose through 24 weeks)