A Randomized Phase 2 Clinical Trial Evaluating Sintilimab and Chidamide in Combination With or Without IBI305 in Patients With Standard Treatment Failure of Advanced or Metastatic pMMR/MSS Colorectal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- The progression-free survival (PFS) rates at 18 weeks
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of sintilimab and chidamide in combination with or without IBI305(bevacizumab) in patients with standard treatment failure of advanced or metastatic pMMR/MSS colorectal adenocarcinoma.
详细描述
In this study, we explored the potential effectiveness of combining PD-1 monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide, with or without IBI305(bevacizumab), in MSS/pMMR unresectable locally advanced or metastatic colorectal cancer patients who failed standard chemotherapy and testified this new combination in preclinical models. Fourty-eight patients were randomized into two groups: the doublet group, who received sintilimab 200 mg every 3 weeks and chidamide 30 mg orally twice weekly, and the triplet group, who received sintilimab, chidamide, and bevacizumab 7.5 mg/kg every 3 weeks.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma.
- •Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR).
- •Subjects must have failed at least two lines of prior treatment.
- •Subjects must have one measurable lesion according to RECIST v1.1 at least.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •18-75 years old.
- •Life expectancy of at least 12 weeks.
- •Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol
排除标准
- •Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or histone deacetylase (HDAC) inhibitor.
- •Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first dose of study medication.
- •Received radiotherapy with 4 weeks of the first dose of study medication.
- •Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture.
- •Known symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Subjects received prior treatment and have stable disease more than 4 weeks from first dose of study medication are permitted to enroll.
- •Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years.
- •Interstitial lung disease requiring corticosteroids.
- •Active or poorly controlled serious infections.
- •Significant malnutrition.
- •Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.
- •Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
- •Within 6 months prior to the enrollment, history of gastrointestinal perforation and/or fistula, gastrointestinal ulcer, bowel obstruction, extensive bowel resection, Crohn's disease, or ulcerative colitis, intra-abdominal abscesses, or long-term chronic diarrhea.
- •History or evidence of inherited bleeding diathesis or coagulopathy or thrombus
- •Any life-threatening bleeding within 3 months prior to the enrollment.
- •High risk of bleeding.
研究组 & 干预措施
The triplet group (sintilimab + chidamide + IBI305)
Every 3 weeks, patients received sintilimab 200 mg and IBI305(bevacizumab) 7.5 mg/kg on day one and chidamide 30 mg orally twice weekly.
干预措施: Sintilimab (Drug)
The triplet group (sintilimab + chidamide + IBI305)
Every 3 weeks, patients received sintilimab 200 mg and IBI305(bevacizumab) 7.5 mg/kg on day one and chidamide 30 mg orally twice weekly.
干预措施: Chidamide (Drug)
The triplet group (sintilimab + chidamide + IBI305)
Every 3 weeks, patients received sintilimab 200 mg and IBI305(bevacizumab) 7.5 mg/kg on day one and chidamide 30 mg orally twice weekly.
干预措施: IBI305 (Drug)
The doublet group (sintilimab + chidamide)
Every 3 weeks, patients received sintilimab 200 mg on day one and chidamide 30 mg orally twice weekly.
干预措施: Sintilimab (Drug)
The doublet group (sintilimab + chidamide)
Every 3 weeks, patients received sintilimab 200 mg on day one and chidamide 30 mg orally twice weekly.
干预措施: Chidamide (Drug)
结局指标
主要结局
The progression-free survival (PFS) rates at 18 weeks
时间窗: 24 months
The proportion of patients without disease progression or death at the 18th week after initiation of the study treatment
次要结局
- Overall Survival (OS);(2 year)
- Disease control rate (DCR)(2 year)
- Duration of response (DoR)(2 year)
- Objective response rate (ORR)(2 year)
- Progression-free survival (PFS);(2 year)
研究者
Rui-hua Xu, MD, PhD
The president of Sun Yat-sen University Cancer Center
Sun Yat-sen University