A Multicenter, Randomized, Open-Label, Blinded-Endpoint Phase II Study of Tolecizumab (a PCSK9 Inhibitor) Enhancing Chemoimmunotherapy as Neoadjuvant Treatment for Patients With pMMR/MSS Locally Advanced Colon Adenocarcinoma (TRIUNITE-08)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 106
- 试验地点
- 1
- 主要终点
- pCR
研究概览
简要总结
This multicenter, randomized, open-label, blinded-endpoint Phase II trial assesses the efficacy and safety of tolecizumab (PCSK9 inhibitor) plus sintilimab/CapeOX chemoimmunotherapy as neoadjuvant treatment for pMMR/MSS locally advanced colon adenocarcinoma (cT3c+). 106 patients are 1:1 randomized to the combination or chemoimmunotherapy alone, with pCR as the primary endpoint.
详细描述
This is a multicenter, randomized, open-label, blinded-endpoint Phase II clinical trial designed to evaluate the efficacy and safety of tolecizumab (a PCSK9 inhibitor) combined with chemoimmunotherapy (sintilimab plus CapeOX regimen) as neoadjuvant treatment for patients with pMMR/MSS locally advanced colon adenocarcinoma (cT3c stage or above). A total of 106 eligible patients will be randomized 1:1 into two arms: Arm A (tolecizumab + sintilimab + CapeOX) and Arm B (sintilimab + CapeOX), both receiving 4 cycles of neoadjuvant therapy. The primary endpoint is the pathological complete response rate (pCR) after treatment; secondary endpoints include major pathological response rate (MPR), objective response rate (ORR), R0 resection rate, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) graded by NCI-CTCAE V5.0. A virtual historical control (single-agent CapeOX neoadjuvant chemotherapy) is set only for sample size calculation. The study will conduct safety follow-up for up to 90 days after the last administration and survival follow-up every 3 months for a total of 3 years, and also collect biological samples for exploratory biomarker analysis to explore the predictive factors of treatment efficacy. All study drugs and related examinations are provided free of charge for participants, and a Data and Safety Monitoring Board (DSMB) is established to monitor the study process and ensure participant safety.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed the written informed consent form and voluntarily participate in the study.
- •Pathohistologically confirmed colon adenocarcinoma with cT3c stage or above. Aged 18 to 80 years, regardless of gender. The lower edge of the tumor is more than 10 cm from the anus. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Sufficient bone marrow, liver, kidney and coagulation functions assessed by laboratory tests (in accordance with the local laboratory reference range).
- •No previous anti-tumor treatment for the current colon cancer (including radiotherapy, chemotherapy, surgery, etc.).
- •No pregnancy or lactation for female patients; male patients agree to take effective contraceptive measures during the study.
排除标准
- •Previous anti-tumor treatment for the current colon cancer. Previous use of PCSK9 inhibitors or PD-1/PD-L1 inhibitors. Active autoimmune diseases or a history of autoimmune diseases. Receiving immunosuppressant or systemic glucocorticoid therapy (except for local low-dose glucocorticoid use).
- •Active infection requiring systemic anti-infective treatment. Severe cardiovascular diseases (e.g., severe hypertension, myocardial infarction, heart failure, etc.).
- •Complicated primary tumor (e.g., tumor perforation, intestinal obstruction without relief after intervention).
- •Pregnant or lactating women. Other conditions that the investigator deems unfit for participation in the study (e.g., poor compliance, severe organ dysfunction, etc.).
研究组 & 干预措施
1.Monoclonal Antibody 2. Immunotherapy 3. Chemotherapy
- Tolecizumab (PCSK9 inhibitor) 600mg, subcutaneous injection, Q6W (Weeks 1,7), total 2 doses
- Sintilimab (PD-1 inhibitor) 200mg, intravenous infusion, Q3W (Weeks1,4,7,10), total 4 cycles
- CapeOX regimen (Oxaliplatin + Capecitabine) Oxaliplatin 130mg/m², IV infusion Q3W (4 cycles); Capecitabine 1000mg/m², oral twice daily, Days1-14 per cycle
干预措施: Tolecizumab (PCSK9 Inhibitor) (Drug)
1.Monoclonal Antibody 2. Immunotherapy 3. Chemotherapy
- Tolecizumab (PCSK9 inhibitor) 600mg, subcutaneous injection, Q6W (Weeks 1,7), total 2 doses
- Sintilimab (PD-1 inhibitor) 200mg, intravenous infusion, Q3W (Weeks1,4,7,10), total 4 cycles
- CapeOX regimen (Oxaliplatin + Capecitabine) Oxaliplatin 130mg/m², IV infusion Q3W (4 cycles); Capecitabine 1000mg/m², oral twice daily, Days1-14 per cycle
干预措施: Sintilimab (Drug)
1. Immunotherapy 2. Chemotherapy
- Sintilimab (PD-1 inhibitor) 200mg, intravenous infusion, Q3W (Weeks1,4,7,10), total 4
- CapeOX regimen (Oxaliplatin + Capecitabine) Oxaliplatin 130mg/m², IV infusion Q3W (4 cycles); Capecitabine 1000mg/m², oral twice daily, Days1-14 per cycle
干预措施: Sintilimab (Drug)
结局指标
主要结局
pCR
时间窗: The pCR rate will be evaluated after surgery, an average of 12 weeks
pCR was defined as the absence, from surgical samples, of malignant cells in the primary site and regional lymph nodes
次要结局
- Disease-free survival(3 years)
- Overall survival (OS)(3 years)
- MPR(From enrollment to 12 Weeks of treatment end)
- Curative resection(Surgical operation assessment)
- Primary tumor downstaging rate(From enrollment to 12 Weeks of treatment end)
- Objective Response Rate (ORR)(After 4 cycles of neoadjuvant therapy (10 weeks))