Anti-PCSK9 Antibody Tafolecimab and Anti-PD-1 Antibody Sintilimab Combined With Neoadjuvant Chemoradiotherapy for pMMR/ MSS Locally Advanced Rectal Cancer : A Prospective, Multicenter, Randomized, Open-Label, Parallel-Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Complete Response (CR) Rate
研究概览
简要总结
This is a randomized, controlled clinical trial based on prior exploratory findings, designed to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with tafolecimab(an anti-PCSK9 inhibitor) and sintilimab (an anti-PD-1 inhibitor) versus neoadjuvant chemoradiotherapy combined with sintilimab alone in patients with pMMR/MSS locally advanced rectal cancer. The primary endpoint is the complete response (CR) rate, including the pathological complete response (pCR) rate in patients who undergo surgery after neoadjuvant therapy, and the clinical complete response (cCR) rate in patients managed with a watch-and-wait strategy. Secondary endpoints include major pathological response (MPR) rate, objective response rate (ORR), downstaging rate, R0 resection rate, tumor regression grade, sphincter preservation rate, disease-free survival (DFS), overall survival (OS), and 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
盲法说明
This is an open-label study. Masking is not feasible because tafolecimab is administered via subcutaneous injection as part of the experimental regimen, while the control group does not receive any subcutaneous injection.
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 to 75 years, any sex.
- •Histologically confirmed rectal adenocarcinoma, determined to be pMMR (proficient mismatch repair) or MSS (microsatellite stable) by immunohistochemistry and/or genetic testing; clinical stage cT3/T4 or cN+; distal tumor margin ≤ 12 cm from the anal verge; and eligible for surgical resection.
- •No evidence of distant metastases.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Adequate hematologic and biochemical function: absolute neutrophil count ≥ 1.5 × 10⁹/L, hemoglobin ≥ 90 g/L, platelets ≥ 100 × 10⁹/L, ALT/AST ≤ 2.5 times the upper limit of normal (ULN), creatinine ≤ 3.0 × ULN.
- •Anticipated good compliance and provision of written informed consent.
排除标准
- •Known allergy or severe adverse reaction to any study drug, including tafolecimab, PD-1 inhibitor (sintilimab), capecitabine, oxaliplatin, or any excipients.
- •Rectal cancer confirmed as dMMR (deficient mismatch repair) or MSI-H (microsatellite instability-high).
- •Pregnant or breastfeeding women, or patients of childbearing potential who refuse to use effective contraception during the study.
- •Other malignancies within the past 5 years, except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, papillary thyroid carcinoma, or other malignancies considered cured after adequate treatment.
- •Prior anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, or local surgical excision.
- •Previous treatment with a PCSK9 inhibitor for any indication.
- •Severe or uncontrolled neurological disease, psychiatric disorder, or cognitive impairment that, in the investigator's judgment, would affect informed consent or protocol adherence.
- •Severe cardiovascular or cerebrovascular disease, including but not limited to: unstable angina, myocardial infarction, coronary revascularization, or stroke within 6 months before enrollment; clinically significant arrhythmia requiring treatment or left ventricular ejection fraction (LVEF) < 50%; New York Heart Association (NYHA) class III or IV heart failure.
- •Active infection requiring long-term systemic therapy (e.g., antibiotics, antivirals, or antifungals).
- •Active autoimmune disease, or requirement for long-term systemic immunosuppressive therapy or corticosteroids (at a dose equivalent to prednisone > 10 mg/day).
- •Known history of human immunodeficiency virus (HIV) infection, or active syphilis, or active pulmonary tuberculosis.
- •Active hepatitis B (HBsAg positive and HBV DNA > 200 IU/mL or > 1000 copies/mL) or active hepatitis C (HCV RNA positive).
- •Any other clinical condition that, in the investigator's opinion, could interfere with study assessments, increase treatment risk, or lead to premature study discontinuation (including but not limited to severe alcohol or drug abuse).
结局指标
主要结局
Complete Response (CR) Rate
时间窗: Within 4 weeks after completion of neoadjuvant therapy for cCR and within 2 weeks after the time of surgery for pCR
Defined as the Proportion of Participants Achieving Pathological Complete Response (pCR) After Surgery or Clinical Complete Response (cCR) Under Watch-and-Wait Strategy Following Neoadjuvant Therapy
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
时间窗: From the first dose of neoadjuvant treatment
次要结局
- Disease-Free Survival (DFS)(approximately 5 years after completion of neoadjuvant chemotherapy)
- Overall Survival (OS)(approximately 5 years after completion of neoadjuvant chemotherapy)
- Major Pathological Response (MPR) Rate(within 2 weeks after the time of surgery)
- Objective Response Rate (ORR)(Within 4 weeks after completion of neoadjuvant therapy or within 2 weeks after surgery;)
- Downstaging Rate(Within 4 weeks after completion of neoadjuvant therapy or within 2 weeks after surgery;)
- Tumor Regression Grade (TRG)(Within 2 weeks after surgery;)
- R0 Resection Rate(Within 2 weeks after surgery;)