Phase Ia/Ib Trial to Evaluate the Tolerability and Safety of IBI101 Monotherapy or in Combination With Sintilimab in Advanced Solid Tumor Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Incicende of Adverse Events (AEs)
研究概览
简要总结
Phase 1a/1b Trial to evaluate the tolerability and safety of IBI101 monotherapy or in combination with Sintilimab in advanced solid tumor patients.
详细描述
IBI101 and Sintilimab will be administered intravenously on Day 1 of every 21-day cycle. The DLT observation period is 21 days starting with the first dose taken on day 1. In the Phase Ia study, eight dose levels of IBI101 (0.01, 0.1, 0.3, 1, 3, 6, 10 and 15mg/kg) will be tested. In the Phase Ib study, four dose levels of IBI101 (1, 3, 6 and 10mg/kg), in combination with Sintilimab 200mg, will be tested. After completion of the dose escalation phase, two combination dose cohorts (IBI101 3mg/kg and 6mg/kg, in combination with Sintilimab 200mg) will be expanded to 10 patients each.
IBI101 is a recombinant fully humanized IgG1 anti-tumor necrosis factor receptor superfamily member 4 (OX40) monoclonal antibody.
Sintilimab is a recombinant fully humanized anti-programmed death 1 (PD1) monoclonal antibody.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients with locally advanced, recurrent or metastatic solid tumors who have failed standard treatment
- •18 to 75 years old
- •Life expectancy ≥ 12 weeks
- •At least 1 measurable lesion
- •ECOG PS score 0 or 1
- •Adequate organ and bone marrow function
排除标准
- •Previous exposure to anti-OX40, anti-PD-1, anti-PD-L1, anti-PD-L2 antibody or other immune checkpoint inhibitors
- •Exposure to any other investigational drug in the 4 weeks prior to 1st dose of investigational drug
- •Exposure to anti-tumor agents in the 3 weeks prior to 1st dose of investigational drug
- •Exposure to immunosuppressant in the 3 weeks prior to 1st dose of investigational drug
- •Major surgery in the 4 weeks prior to 1st dose of investigational drug
- •30Gy radiation in the chest in the 6 months prior to 1st dose of investigational drug
- •History of autoimmune disease
- •Symptomatic CNS metastasis
研究组 & 干预措施
IBI101
IBI101 will be administrated intravenously. 3+3 dose escalation design will be used with eight dose levels being tested.
干预措施: IBI101 (Drug)
IBI101 in combination with Sintilimab
IBI101 and Sintilimab will be administrated intravenously. 3+3 dose escalation design will be used with 4 dose levels of IBI101 being tested.
Two dose levels of IBI101 in combination with Sintilimab will be expanded to 10 patients each.
干预措施: IBI101 (Drug)
IBI101 in combination with Sintilimab
IBI101 and Sintilimab will be administrated intravenously. 3+3 dose escalation design will be used with 4 dose levels of IBI101 being tested.
Two dose levels of IBI101 in combination with Sintilimab will be expanded to 10 patients each.
干预措施: Sintilimab (Drug)
结局指标
主要结局
Incicende of Adverse Events (AEs)
时间窗: 2 years
Number of patients with AE, treatment-related AE (TRAE), immune-related AEs (irAE), AE of special interest (AESI), serious adverse event (SAE), discontinuation of study drug due to AE, dose-limiting toxicity (DLT) assessed by CTCAE v5.0.
次要结局
- Total body clearance (CL)(2 years)
- Overall response rate (ORR)(2 years)
- Time to response (TTR)(2 years)
- Progression free survival (PFS)(2 years)
- Mean residue time (MRT)(2 years)
- OX40 receptor occupancy(2 years)
- Duration of response (DOR)(2 years)
- Time at which maximum concentration occurred (Tmax)(2 years)
- Area Under Curve (AUC)last and AUC0-inf(2 years)
- Maximum Concentration (Cmax)(2 years)
- Volume of distribution (Vz)(2 years)
- Elimination half-life (t1/2)(2 years)
- Anti-drug antibody (ADA)(2 years)
- Neutralizing antibody (Nab) positive rate(2 years)
- T cell subset analysis(2 years)