The Multicenter, Open-label, Single-arm, Multi-cohort Phase Ib/II Clinical Study to Evaluate the Efficacy and Safety of JSKN016 in Combination Therapy in Chinese Participants With Inoperable Locally Advanced or Metastatic HER2-negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Objetctive Response Rate (ORR)
研究概览
简要总结
This study aims to evaluate the safety and effectiveness of JSKN016 in combination with different treatments for patients with HER2-negative breast cancer that cannot be removed by surgery or has spread to other parts of the body. The study includes four groups of patients based on treatment history and tumor characteristics. Each group will receive JSKN016 with chemotherapy or immunotherapy. The goal is to find out how well the treatment works and how safe it is.
详细描述
This clinical study investigates the safety and efficacy of JSKN016 combined with various therapies for patients with advanced, inoperable, or metastatic HER2-negative breast cancer. The study includes four groups with different treatment regimens, targeting HR+HER2-negative breast cancer and triple-negative breast cancer (TNBC) with varying prior treatments. Participants will receive JSKN016 in combination with paclitaxel, capecitabine, eribulin, or pembrolizumab. The primary endpoint is the objective response rate (ORR) based on RECIST 1.1 criteria. The secondary endpoints include efficacy, safet, and other related outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of understanding and signing the informed consent form.
- •Aged ≥18 and ≤75 years, regardless of sex.
- •Histologically or cytologically confirmed inoperable locally advanced or metastatic HER2-negative breast cancer.
- •Hormone receptor-positive participants with progression/intolerance after standard endocrine therapy, or unsuitable for it.
- •Disease progression confirmed by radiological evidence post-systemic treatment.
- •Available archived or newly obtained tumor tissue/biopsy.
- •No prior systemic therapy for advanced disease, except for prior endocrine ± targeted therapy or CDK4/6 inhibitors.
- •Measurable non-CNS lesion per RECIST 1.
- •Expected survival ≥3 months.
- •ECOG performance status of 0 or
- •Contraceptive use agreement for fertile participants.
- •Adequate organ function within 7 days of enrollment:
- •Bone marrow: ANC ≥1.5 × 10⁹/L, Hemoglobin ≥90 g/L, Platelets ≥100 × 10⁹/L.
- •Liver: Bilirubin ≤1.5 × ULN, ALT/AST ≤3 × ULN.
- •Renal: Creatinine ≤1.5 × ULN or Ccr ≥60 mL/min.
- •Coagulation: INR/PT ≤1.5 × ULN, APTT ≤1.5 × ULN.
排除标准
- •CNS metastasis (except stable cases treated with radiation or surgery).
- •Unstable spinal cord compression or untreated history.
- •Recent live vaccine (except seasonal flu vaccines).
- •Recent anti-tumor treatment within 28 days or 5 half-lives (whichever is shorter).
- •Recent palliative therapy within 14 days.
- •Major surgery within 28 days or planned during the study.
- •Severe gastrointestinal issues or recent major GI bleeding.
- •Uncontrolled pleural/peritoneal effusions or cachexia.
- •Prior HER3/TROP2-targeted therapy or topoisomerase I inhibitors.
- •Other malignancies within 5 years (except certain skin or localized cancers).
- •Current interstitial lung disease or uncontrolled infections.
- •Severe hypercalcemia or uncontrolled cancer-related pain.
- •Autoimmune diseases, unless stable with treatment.
- •Uncontrolled comorbidities (e.g., active infections, cardiovascular issues).
- •Toxicities from previous treatments not resolved to CTCAE ≤
- •Recent steroid use or need for systemic immunosuppressive therapy.
- •Allergy to study drug components.
- •Pregnancy or breastfeeding.
研究组 & 干预措施
Cohort 2: JSKN016+Capecitabine
JSKN016 (5mg/kg IV Q3W D1) + capecitabine (1000mg/m² PO BID Q3W D1-14)
干预措施: JSKN016 (Drug)
Cohort 1: JSKN016+Paclitaxel
JSKN016 (5mg/kg IV Q3W D1) + nab-paclitaxel (125mg/m² IV Q3W D1, D8)
干预措施: JSKN016 (Drug)
Cohort 1: JSKN016+Paclitaxel
JSKN016 (5mg/kg IV Q3W D1) + nab-paclitaxel (125mg/m² IV Q3W D1, D8)
干预措施: Paclitaxel (albumin bound) (Drug)
Cohort 2: JSKN016+Capecitabine
JSKN016 (5mg/kg IV Q3W D1) + capecitabine (1000mg/m² PO BID Q3W D1-14)
干预措施: Capecitabine (Drug)
Cohort 3: JSKN016+Eribulin
JSKN016 (5mg/kg IV Q3W D1) + eribulin (1.4mg/m² IV Q3W D1, D8)
干预措施: JSKN016 (Drug)
Cohort 3: JSKN016+Eribulin
JSKN016 (5mg/kg IV Q3W D1) + eribulin (1.4mg/m² IV Q3W D1, D8)
干预措施: Eribulin (Drug)
Cohort 4: JSKN016+Pembrolizumab/Toripalimab
JSKN016 (5mg/kg IV Q3W D1) + pembrolizumab (200mg IV Q3W D1) or toripalimab (240mg IV Q3W D1).
干预措施: JSKN016 (Drug)
Cohort 4: JSKN016+Pembrolizumab/Toripalimab
JSKN016 (5mg/kg IV Q3W D1) + pembrolizumab (200mg IV Q3W D1) or toripalimab (240mg IV Q3W D1).
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Objetctive Response Rate (ORR)
时间窗: From baseline until disease progression, death, or end of treatment, whichever occurs first (up to approximately 24 months)
The proportion of participants who achieve a confirmed complete response (CR) or partial response (PR), as assessed by investigators according to RECIST v1.1 criteria.
次要结局
- Overall Survival (OS)(From first dose to death (up to approximately 36 months))
- Duration of Response (DoR)(From first documented response to progression or death (up to approximately 24 months))
- Disease Control Rate (DCR)(From baseline to disease progression or end of treatment (up to approximately 24 months))
- Progression-Free Survival (PFS)(From first dose until disease progression or death (up to approximately 24 months))
- Frequency and Severity of Adverse Events (AEs)(From first dose through 30 days after the last dose of study treatment (up to approximately 30 months))