A Phase Ib/II , Open-label , Investigator-initiated Trail of An Anti-PD-1 Inhibitor SHR-1210 in Combination With A CDK4/6 Inhibitor SHR6390 in Patients With Advanced Colorectal Cancer, Non-small Cell Lung Cancer and Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 41
- 主要终点
- ORR(phase II)
研究概览
简要总结
This is a Phase Ib/II , Open-label , Investigator-initiated Trail of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With SHR6390 (a CDK4/6 Inhibitor) in Patients With Advanced Colorectal Cancer, Non-small Cell Lung Cancer and Hepatocellular Carcinoma.
The study was designed in two stages, the first stage was the tolerance observation stage, and the second stage was the curative effect expansion stage.
The first part of the study is the Dose-finding Phase designed to establish the safety of SHR-1210 Combination With SHR6390 at different dose Levels(150mg QD or 100mg QD ). The second part of the study is the Expansion Phase designed to generate additional clinical data at specified doses .
This study aims to evaluate the safety and efficacy of SHR-1210 combination with SHR6390 in the treatment of advanced CRC,NSCLC and HCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Subjects voluntarily participate in this study and sign informed consent .
- •Men or women aged 18-75 years
- •Has confirmed by histology and cytology advanced and/or metastatic colorectal cancer patients, the advanced (Ⅲ B/Ⅳ period) in non-small cell lung cancer，Or patients with advanced hepatocellular carcinoma confirmed histologically or cytologically or clinically，At least one measurable lesion that meets the RECIST v1.1 criteria without local treatment.
- •The patients can swallow pills normally.
- •ECOG score was 0 or
- •Have a life expectancy of at least 12 weeks.
- •The functions of vital organs meet the following requirements (excluding the use of any blood components and cytokines during screening) : Neutrophils≥1.5 x 109/L, Hb≥9g/dL; Plt≥90 x 109/L, ALB≥3g/dL, TSH≤ULN(Upper Limit Of Norma), TBIL ≤ 1.25 x ULN, ALT and AST ≤ 1.5 x ULN, AKP≤ 2.5 x ULN, CR≤ 1.5 x ULN
- •Female Subjects of childbearing potential must have a negative serum pregnancy test within 72 hours before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 3 months after the last dose of study treatment.
排除标准
- •Subjects had any active autoimmune disease or history of autoimmune disease.
- •Subjects are using immunosuppressive agents, or systemic, or absorptive,local hormone therapy to achieve immunosuppression. It is still in use within 2 weeks before enrollment.
- •Subjects with severe allergic reactions to other monoclonal antibodies.
- •The subjects had a central nervous system metastases of clinical symptoms.
- •Central lung squamous cell carcinoma, or NSCLC with large vascular invasion confirmed by imaging.
- •A heart condition or disease that is not well controlled.
- •Subjects had active infections.
- •Other clinical trials of drugs were used within 4 weeks prior to the first administration.
- •The subjects have received other PD-1 antibody therapy or other immunotherapy for PD-1 / PD-L1 or CDK4/6 inhibitor treatment in the past.
- •There are other factors lead to patients can not participate in this clinical study by the judgment of the investigator.
研究组 & 干预措施
SHR-1210 + SHR6390
SHR-1210 was administered 200mg iv every 2 weeks in combination with SHR6390 150mg or 100mg oral daily with 3 weeks on and 1 week off
干预措施: SHR-1210 (Drug)
SHR-1210 + SHR6390
SHR-1210 was administered 200mg iv every 2 weeks in combination with SHR6390 150mg or 100mg oral daily with 3 weeks on and 1 week off
干预措施: SHR6390 (Drug)
结局指标
主要结局
ORR(phase II)
时间窗: from the first drug administration up to two years
Overall Response Rate
MTD /DLT (phase Ib)
时间窗: Within four weeks after dosing
Maximum Tolerated Dose/Dose Limiting Toxicity
次要结局
- Incidence of Treatment-Emergent Adverse Events (phase Ib/II)(from the first drug administration to within 90 days for the last SHR-1210 dose)
- DoR (phase Ib/II)(from the first drug administration up to two years)
- ORR(phase Ib)(from the first drug administration up to two years)
- CBR (phase Ib/II)(from the first drug administration up to last patients treatment for 6 months.)
- PFS(phase Ib/II)(from the first drug administration up to two years)
- 12m-OS(12 months after the first drug administration)
- TTR(phase Ib/II)(from the first drug administration up to one year)
研究者
Yanqiao Zhang
Director of the hospital
Harbin Medical University