FOLFIRI Plus Bevacizuamb With or Without Iparomlimab and Tuvonralimab as Second-Line Treatment for Metastatic Colorectal Cancer: A Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 270
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Thsi study is a randomised, parallel-controlled phase II/III trial evaluating FOLFIRI plus bevacizumab with or without QL1706 as second-line therapy for metastatic colorectal cancer. The primary endpoint is PFS. Secondary endpoint includes overall survival, objective response rate, safety profiles, immune-related adverse events, and patient quality of life. Exploratory analyses focus on dynamic shifts in tumour immune microenvironment and biomarkers, aiming to identify predictive signatures for therapeutic efficacy and immune toxicities.
详细描述
This is a prospective, randomised, parallel-controlled phase II/III clinical trial designed to investigate the efficacy and safety of adding QL1706, a dual PD-1/CTLA-4 bispecific immune checkpoint inhibitor, to the standard second-line FOLFIRI plus bevacizumab regimen in patients with metastatic colorectal cancer. Eligible participants who have progressed after first-line oxaliplatin-based systemic therapy will be randomly assigned to either the experimental group receiving combination treatment with FOLFIRI, bevacizumab and QL1706 or the control group treating with FOLFIRI plus bevacizumab alone, to conduct head-to-head comparative analysis of clinical outcomes. The primary endpoint of the trial is progression-free survival. Secondary endpoints comprehensively evaluating overall survival, objective response rate, disease control rate, the incidence and severity of treatment-related adverse events and immune-related adverse events. Exploratory analyses are pre-specified in this trial. Serial detection and dynamic analysis of tumour immune microenvironment characteristics and multiple peripheral biomarkers will be performed to clarify the immunomodulatory effect of the triple combination regimen. Furthermore, correlative analyses will be conducted to screen and validate potential predictive signatures, including immune cell subsets, cytokine profiles and molecular biomarkers, for clinical treatment response and immune-related toxicities, aiming to provide precise evidence for individualised second-line immunotherapy combined with targeted chemotherapy for metastatic colorectal cancer.
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
None (open label)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Willing and able to provide written informed consent.
- •Age ≥ 18 years old. 3.Histologically confirmed metastatic colorectal adenocarcinoma with pMMR/MSS status.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •5.Discontinued first-line oxaliplatin-based doublet chemotherapy for metastatic colorectal cancer due to intolerable toxicities or disease progression; OR developed recurrent metastatic disease within 6 months after the last dose of adjuvant chemotherapy. 6.Presence of evaluable lesions on imaging examinations.
- •Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment. 8.Willing and able to comply with study procedures and scheduled visit schedules
排除标准
- •1.Patients complicated with digestive tract diseases including duodenal ulcer, ulcerative colitis, intestinal obstruction, or other conditions judged by the investigator to potentially cause gastrointestinal hemorrhage or perforation; or massive pleural effusion or ascites requiring intervention. 2.Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
- •Radiological evidence of brain metastases.
- •Prior treatment with irinotecan hydrochloride, or prior receipt of PD-1 and/or CTLA-4 immunotherapy in the first-line setting.
- •Autoimmune diseases requiring continuous systemic steroid therapy.
- •History of laparotomy, thoracotomy or intestinal resection within 28 days prior to enrollment; or unhealed wounds (excluding suture wounds from central venous catheter implantation), gastrointestinal ulcers or traumatic fractures.
- •Any of the following events occurring within 12 months before study enrollment: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) class ≥ 2 cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure. 8.Confirmed human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related diseases.
- •Active inflammatory bowel disease or other colorectal diseases causing chronic diarrhea; interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes mellitus, hypertension, pulmonary fibrosis, acute pneumonia, etc.).
- •Breastfeeding or pregnant women; lack of effective contraceptive.
- •Other severe physical or psychiatric illnesses, or laboratory abnormalities that may increase the risks of study participation or interfere with study outcomes; or patients deemed unsuitable for this study by the investigator.
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 2 years
The PFS is defined as the time from the start of treatment to the date of first documented PD or death as a result of any cause, whichever occurred first.
次要结局
- Objective response rate (ORR)(2 years)
- Overall Survival (OS)(5 years)
- Toxicity assessed using the NCI common toxicity criteria, version 5.0.(2 years)
研究者
Yanhong Deng
Professor
Sun Yat-sen University