A Phase II Clinical Study to Evaluate the Efficacy and Safety of KC1036 Combined With PD-1 Antibody and Platinum-based Chemotherapy as First-line Treatment for Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 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 efficacy and safety of KC1036 in combination with PD-1 antibody and platinum-based chemotherapy as a first-line treatment for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).
详细描述
This multicenter Phase II study evaluates KC1036 in combination with PD-1 antibody and platinum-based chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma. The trial comprises a Phase IIa dose-escalation and expansion phase to assess the safety of KC1036 at 20, 30, or 40 mg QD, followed by a Phase IIb randomized evaluation of 2-3 cohorts (up to 50 subjects per arm) to identify the recommended Phase III dose. Subjects receive daily oral KC1036 plus toripalimab, paclitaxel, and cisplatin every 3 weeks until confirmed disease progression assessed by the RECIST V1.1 standard, death, intolerable toxicity, initiation of a new anti-tumor therapy, other reasons leading to treatment discontinuation as specified by protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Males or females aged 18 to 75 years;
- •Histologically or cytologically confirmed esophageal or esophageal-gastric junction squamous cell carcinoma;
- •Patients who have not received prior systemic anti-tumor therapy for the current recurrent or metastatic disease;
- •At least one measurable tumor lesion according to RECIST 1.1;
- •Eastern Cooperative Oncology Group performance status score of 0 or 1;
- •Life expectancy > 12 weeks;
- •BMI≥16.0 kg/m2;
- •Adequate bone marrow, renal, and hepatic function;
- •Female patients of childbearing potential with a negative blood pregnancy test completed within 7 days before the first dose;
- •Patients should participate in the study voluntarily and sign informed consent.
排除标准
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastasis;
- •Other malignancies within the past 5 years;
- •Known hypersensitivity to any monoclonal antibodies or chemotherapy components;
- •Gastrointestinal abnormalities;
- •High risk of bleeding or fistula due to tumor invasion of adjacent organs, or existing esophageal/tracheal fistula;
- •Cardiovascular and cerebrovascular diseases;
- •Prior therapy with anti-angiogenic drugs or immunotherapy; Systemic therapy, investigational drugs, or live vaccines within 4 weeks prior to the first dose; Palliative radiotherapy within 2 weeks or major surgery within 28 days prior to enrollment;
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- •Presence of unresolved toxicities from prior anti-tumor therapy, defined as having not resolved to NCI CTCAE 5.0 Grade 0 or 1;
- •Active autoimmune disease or a history of autoimmune disease requiring systemic treatment;
- •Active infections, including severe infection (CTCAE > Grade 2) within 4 weeks, active tuberculosis, or positive status for HIV, HBV, or HCV;
- •Pregnant or lactating women;
- •Female subjects of child-bearing potential and male subjects of reproductive capacity who do not agree to use contraceptive measures during the study and for 6 months after the end of the study;
- •Other conditions assessed by the investigator that would increase safety risks or interfere with the study results.
研究组 & 干预措施
Phase IIa (Dose Escalation and Expansion)
This is a multicenter, single-arm, dose-escalation and expansion phase. Subjects will receive KC1036 at one of three dose levels (20 mg QD, 30 mg QD, or 40 mg QD) in combination with fixed doses of Toripalimab and platinum-based chemotherapy (Paclitaxel and Cisplatin).
干预措施: KC1036 (Drug)
Phase IIa (Dose Escalation and Expansion)
This is a multicenter, single-arm, dose-escalation and expansion phase. Subjects will receive KC1036 at one of three dose levels (20 mg QD, 30 mg QD, or 40 mg QD) in combination with fixed doses of Toripalimab and platinum-based chemotherapy (Paclitaxel and Cisplatin).
干预措施: Toripalimab (Drug)
Phase IIa (Dose Escalation and Expansion)
This is a multicenter, single-arm, dose-escalation and expansion phase. Subjects will receive KC1036 at one of three dose levels (20 mg QD, 30 mg QD, or 40 mg QD) in combination with fixed doses of Toripalimab and platinum-based chemotherapy (Paclitaxel and Cisplatin).
干预措施: Paclitaxel (Drug)
Phase IIa (Dose Escalation and Expansion)
This is a multicenter, single-arm, dose-escalation and expansion phase. Subjects will receive KC1036 at one of three dose levels (20 mg QD, 30 mg QD, or 40 mg QD) in combination with fixed doses of Toripalimab and platinum-based chemotherapy (Paclitaxel and Cisplatin).
干预措施: Cisplatin (Drug)
Phase IIb (Randomized Expansion)
This is a multicenter, randomized, parallel-group, open-label phase. Based on Phase IIa results, 2-3 dose cohorts will be selected. Subjects will be randomized (1:1 or 1:1:1) to receive the assigned dose of KC1036 in combination with Toripalimab and platinum-based chemotherapy.
干预措施: Toripalimab (Drug)
Phase IIb (Randomized Expansion)
This is a multicenter, randomized, parallel-group, open-label phase. Based on Phase IIa results, 2-3 dose cohorts will be selected. Subjects will be randomized (1:1 or 1:1:1) to receive the assigned dose of KC1036 in combination with Toripalimab and platinum-based chemotherapy.
干预措施: Paclitaxel (Drug)
Phase IIb (Randomized Expansion)
This is a multicenter, randomized, parallel-group, open-label phase. Based on Phase IIa results, 2-3 dose cohorts will be selected. Subjects will be randomized (1:1 or 1:1:1) to receive the assigned dose of KC1036 in combination with Toripalimab and platinum-based chemotherapy.
干预措施: Cisplatin (Drug)
Phase IIb (Randomized Expansion)
This is a multicenter, randomized, parallel-group, open-label phase. Based on Phase IIa results, 2-3 dose cohorts will be selected. Subjects will be randomized (1:1 or 1:1:1) to receive the assigned dose of KC1036 in combination with Toripalimab and platinum-based chemotherapy.
干预措施: KC1036 (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Baseline to study completion (approximately 24 months)
ORR is defined as the proportions of patients with a complete response (CR) or partial response (PR) according to RECIST 1.1.
次要结局
- Progression-free survival (PFS)(Baseline to study completion (approximately 24 months))
- Disease Control Rate (DCR)(Baseline to study completion (approximately 24 months))
- Duration of Response (DOR)(Baseline to study completion (approximately 24 months).)
- TTR(Baseline to study completion (approximately 24 months))
- Adverse events (AEs)(Baseline to 30 days after the last dose of study treatment)