A Phase II, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of SKB500 Combinations in Patients With Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 23
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and preliminary antitumor activity of SKB500 combinations in patients with Esophageal Squamous Cell Carcinoma. The study is divided into three parts: the safety run-in phase, randomized enrollment phase and cohort expansion phase.
详细描述
This is a Phase II, multicenter, open-label study to evaluate the safety, tolerability and preliminary antitumor activity of SKB500 combinations in patients with Esophageal Squamous Cell Carcinoma. The study is divided into three parts: the safety run-in phase, randomized enrollment phase and cohort expansion phase.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years and ≤75 years
- •Histologically or cytologically confirmed unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC), who are ineligible for curative-intent therapies:
- •Safety run-in phase (Cohort 1, 2 and 3): received no more than 1 prior line of systemic therapy for locally advanced or metastatic ESCC.
- •Safety run-in phase (Cohort 4), randomized enrollment phase and cohort expansion phase: no prior systemic therapy for locally advanced or metastatic ESCC.
- •Participants are required to provide tumor tissue samples for biomarker analysis.
- •Has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy ≥ 12 weeks.
排除标准
- •Histology or cytology confirms the presence of concurrent adenocarcinoma components.
- •Leptomeningeal, brainstem, spinal, spinal cord compression, or active CNS metastases.
- •Risk of esophagotracheal/esophagopleural fistula, or symptomatic invasion/compression of vital organs/major blood vessels.
- •Active autoimmune disease requiring systemic therapy within past 2 years.
- •Weight loss ≥10% within 4 weeks prior to the first dose, or Nutritional Risk Index (NRI) < 83.
- •Severe infection within 4 weeks or active infection requiring systemic treatment within 2 weeks pre-dose.
- •Uncontrolled comorbidities (e.g., decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, Grade ≥2 peripheral neuropathy).
- •Cardiovascular/cerebrovascular events within 6 months pre-dose (e.g., Myocardial Infarction, unstable angina, acute/persistent ischemia, Grade 3/4 Heart Failure, symptomatic/uncontrolled arrhythmia, Cerebrovascular Accident, Transient Ischemic Attack).
- •Uncontrolled hypertension, diabetes, or recurrent pleural/pericardial/abdominal effusion requiring drainage.
- •History of interstitial lung disease (ILD) or noninfectious pneumonitis that require steroid treatment, or currently has ILD/noninfectious pneumonitis.
- •Unresolved to grade ≤ 1 of prior anti-cancer treatment toxicities criteria per CTCAE v6.
- •Previously received B7-H3-targeted agents, including antibody, antibodydrug conjugate (ADC), and other agents.
- •Previously received treatment with an ADC that consists of a topoisomerase l inhibitor.
- •Pregnant or lactating women.
研究组 & 干预措施
Cohort 2. SKB500+Tislelizumab+5-FU
Participants will receive Tislelizumab followed by SKB500, 5-FU
干预措施: SKB500 (Drug)
Cohort 1. SKB500+Tislelizumab
Participants will receive Tislelizumab followed by SKB500
干预措施: SKB500 (Drug)
Cohort 1. SKB500+Tislelizumab
Participants will receive Tislelizumab followed by SKB500
干预措施: Tislelizumab (Drug)
Cohort 2. SKB500+Tislelizumab+5-FU
Participants will receive Tislelizumab followed by SKB500, 5-FU
干预措施: Tislelizumab (Drug)
Cohort 2. SKB500+Tislelizumab+5-FU
Participants will receive Tislelizumab followed by SKB500, 5-FU
干预措施: 5 - FU (Drug)
Cohort 3. SKB500+Tislelizumab+ Cisplatin
Participants will receive Tislelizumab followed by SKB500, Cisplatin
干预措施: SKB500 (Drug)
Cohort 3. SKB500+Tislelizumab+ Cisplatin
Participants will receive Tislelizumab followed by SKB500, Cisplatin
干预措施: Tislelizumab (Drug)
Cohort 3. SKB500+Tislelizumab+ Cisplatin
Participants will receive Tislelizumab followed by SKB500, Cisplatin
干预措施: Cisplatin (Drug)
Cohort 4. SKB500+Tislelizumab+ Cisplatin+5-FU
Participants will receive Tislelizumab followed by SKB500, Cisplatin, 5-FU
干预措施: SKB500 (Drug)
Cohort 4. SKB500+Tislelizumab+ Cisplatin+5-FU
Participants will receive Tislelizumab followed by SKB500, Cisplatin, 5-FU
干预措施: Tislelizumab (Drug)
Cohort 4. SKB500+Tislelizumab+ Cisplatin+5-FU
Participants will receive Tislelizumab followed by SKB500, Cisplatin, 5-FU
干预措施: Cisplatin (Drug)
Cohort 4. SKB500+Tislelizumab+ Cisplatin+5-FU
Participants will receive Tislelizumab followed by SKB500, Cisplatin, 5-FU
干预措施: 5 - FU (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: up to 24 months
Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by investigator based on RECIST version 1.1.
Incidence and severity of adverse events (AEs) and serious adverse event(SAEs)
时间窗: up to 24 months
Incidence and severity of adverse events (AEs) and serious adverse event(SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v6.0, as well as clinically significant abnormal laboratory findings.
次要结局
- Progression-free survival (PFS)(up to 24 months)
- Duration of response (DOR)(up to 24 months)
- Disease control rate (DCR)(up to 24 months)
- Overall Survival (OS)(up to 24 months)
- Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of SKB500-ADC, SKB500-TAB and free payload(up to 24 months)
- Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of SKB500-ADC, SKB500-TAB and free payload(up to 24 months)
- Anti-drug Antibodies (ADA) for SKB500(up to 24 months)