A Multicenter, Randomized, Two-arm, Open-label, Blinded Endpoint, Phase II Study of PCSK9 Inhibitor Tafolecimab Combined With Sintilimab and CapeOX Chemotherapy as Neoadjuvant Treatment for pMMR/MSS Locally Advanced Colon Cancer (TRIUNITE-08)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 70
- 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 .
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.).
- •Fasting LDL-C <1.0 mmol/L (39 mg/dL), only excluding extremely low levels (suggestive of cachexia/severe hepatic disease)
- •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. Immunotherapy 2. Chemotherapy
1. Sintilimab (PD-1 inhibitor) 200mg, intravenous infusion, Q3W (Weeks1,4,7,10), total 4 2. 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.Tafolecimab 2. Immunotherapy 3. Chemotherapy
Tafolecimab 600mg SC Q6W (Weeks 1, 7) + Sintilimab 200mg IV Q3W (Weeks 1, 4, 7, 10) + Oxaliplatin 130mg/m² IV Q3W (Weeks 1, 4, 7, 10) + Capecitabine 1000mg/m² PO BID Days 1-14 of each cycle, 4 cycles total. Arm B (Active Comparator): Sintilimab 200mg IV Q3W (Weeks 1, 4, 7, 10) + Oxaliplatin 130mg/m² IV Q3W (Weeks 1, 4, 7, 10) + Capecitabine 1000mg/m² PO BID Days 1-14 of each cycle, 4 cycles total.
干预措施: Sintilimab (Drug)
1.Tafolecimab 2. Immunotherapy 3. Chemotherapy
Tafolecimab 600mg SC Q6W (Weeks 1, 7) + Sintilimab 200mg IV Q3W (Weeks 1, 4, 7, 10) + Oxaliplatin 130mg/m² IV Q3W (Weeks 1, 4, 7, 10) + Capecitabine 1000mg/m² PO BID Days 1-14 of each cycle, 4 cycles total. Arm B (Active Comparator): Sintilimab 200mg IV Q3W (Weeks 1, 4, 7, 10) + Oxaliplatin 130mg/m² IV Q3W (Weeks 1, 4, 7, 10) + Capecitabine 1000mg/m² PO BID Days 1-14 of each cycle, 4 cycles total.
干预措施: Tafolecimab (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)
- MPR (Major Pathological Response)(MPR rate assessed postoperatively, at an average of 12 weeks)
- Overall survival (OS)(3 years)
- Primary tumor downstaging rate(From enrollment to 12 Weeks of treatment end)
- R₀ （Curative） resection(Surgical operation assessment)
- Objective Response Rate (ORR)(After 4 cycles of neoadjuvant therapy (10 weeks))
- Radiological response based on RECIST 1.1 criteria: CR, PR, SD, PD(From enrollment to 12 Weeks of treatment end)