A Phase II Study of Sacituzumab Tirumotecan (Sac-TMT) Combined With Tagitanlimab(KL-A167) in PD-L1-Positive, Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer Patients Previously Treated With CDK4/6 Inhibitors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- progression-free survival rate (PFS)
研究概览
简要总结
This is a Phase II single-arm study designed to evaluate the efficacy and safety of Sac-TMT + KL-A167 in 35 patients with PD-L1+, HR+/HER2- metastatic breast cancer who previously treated with CDK4/6 inhibitor. The primary endpoint is the 6-month PFS rate. Treatment will continue until disease progression or intolerable toxicity, with periodic imaging assessments and survival follow-up.
详细描述
This study is a prospective, single-arm, multicenter Phase II study designed to evaluate the efficacy and safety of Sac-TMT in combination with KL-A167 for the treatment of PD-L1-positive, HR+/HER2- metastatic breast cancer patients who previously treated with CDK4/6.
The study plans to enroll 35 patients. The primary endpoint is the 6-month progression-free survival (PFS) rate assessed by the investigator (RECIST v1.1). Secondary endpoints include PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety. An exploratory endpoint is to analyze the correlation between TROP2 and PD-L1 expression and efficacy.
The treatment regimen consists of intravenous administration of Sac-TMT (5 mg/kg, Q2W) combined with KL-A167 (900 mg, Q2W). Treatment will continue until disease progression or occurrence of intolerable toxicity. Tumor assessments will be conducted every 6 weeks for the first 6 months, followed by every 12 weeks thereafter. Safety follow-up will occur after treatment completion, with telephone follow-ups every 3 months to collect survival and subsequent treatment information.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •18-75 years old.
- •HR+/HER2- breast cancer (BC), meeting the following conditions:
- •HR+/HER2-; HER2-(IHC 0 or 1+); IHC 2+(FISH negative); HR+ (ER and/or PR IHC showed ≥1%);
- •Tumor stage: Locally advanced, recurrent, or metastatic HR+/HER2- breast cancer; 3) Disease progression during or within 12 months after completion of adjuvant endocrine therapy based on a CDK4/6 inhibitor, or disease progression on CDK4/6 inhibitor treatment for metastatic disease; 4) PD-L1 positive (CPS ≥ 1); 5) At least one measurable target lesion as assessed by the investigator per RECIST 1.1; 6) Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy more than 12 weeks; 7) Adequate organ function, defined as:
- •Complete blood count: Neutrophil count ≥ 1.5×10^9/L; platelets ≥ 100×10^9/L; hemoglobin ≥ 9 g/dL.
- •Liver function: AST, ALT, and ALP ≤ 2.5× ULN; total bilirubin ≤ 1.5× ULN; ALT and AST ≤ 5× ULN, TBIL ≤ 2× ULN for patients with liver metastases; ALP ≤ 5× ULN for patients with liver or bone metastases.
- •Renal function: Creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula).
- •Coagulation function: INR, APTT, and PT ≤ 1.5× ULN.
- •Cardiac function: ECHO or MUGA scan indicating LVEF ≥ 50%. 8) For female participants of childbearing potential and male participants with reproductive potential, effective medical contraceptive measures must be implemented from the time of signing the informed consent until six months after the last administration; 9) Voluntary participation in the study with signed informed consent, demonstrated good compliance, and willingness to follow up as required.
排除标准
- •Received any of the following treatments during the advanced stage:
- •.Chemotherapy;
- •.any targeted therapy against topoisomerase I including antibody-drug conjugates (ADCs);
- •. immune checkpoint agonists (e.g., anti-PD-1/L1antibodies, anti-CTLA-4 antibodies), or any immune cell therapy;
- •Recurrence or metastasis within 12 months of the last chemotherapy in the early stage;
- •Subjects with central nervous system (CNS) metastases. For subjects with brain metastases who have previously received local therapy,
- •Other malignancies within 5 years prior to dosing (excluding locally treated and cured tumors such as basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ);
结局指标
主要结局
progression-free survival rate (PFS)
时间窗: 6 months
The proportion of subjects who remained free of radiographic disease progression or death within 6 months of receiving the first dose of study treatment, relative to the total number of subjects.
次要结局
- Overall survival (OS)(1 year)
- Objective Response Rate (ORR)(1 year)
- Progression-Free Survival (PFS)(1 year)
- Disease Control Rate (DCR)(1 year)
- Duration of Response (DoR)(1 year)
研究者
Xu fei
Associate Chief Physician
Sun Yat-sen University