A Phase I Clinical Study to Evaluate the Tolerability, Safety, Pharmacokinetics and Efficacy of SHR-1501 in Combination With SHR-1316 in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 5
- 主要终点
- Dose-limiting toxicity and Maximum tolerated dose
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of SHR-1501 in combination with SHR-1316 in patients with advanced malignancies and to provide a recommended dose (RP2D) for subsequent clinical studies.
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
- •All Patients All patients must meet all the following criteria to be eligible to participate:
- •Voluntarily participate in this clinical study, understand the research procedure and be able to sign informed consent in writing;
- •Subjects must be willing and able to follow the research protocol;
- •Aged 18-75 years old when the informed consent form is signed;
- •Have a histologically or cytologically confirmed diagnosis of advanced or metastatic tumor malignancy;
- •Patients' malignancies must be relapsed or refractory to standard treatment, or patients cannot tolerate standard treatment, or patients have actively refused standard therapy;
- •FFPE tumor tissue or unstained slides of tumor sample must be obtained from patients enrolled in the dose expansion or indication expansion stage, both preserved samples collected within 6 months before the first dose (or up to 12 months prior to the first dose) and fresh samples (preferred) are acceptable;
- •Eastern Cooperative Oncology Group ECOG PS score of 0-1;
- •Have a life expectancy of ≥ 12 weeks;
- •Adequate organ function defined according to the protocol, These results should be completed within 14 days prior to the first study treatment:
- •Non-surgically sterilized women of childbearing age or male subjects are required to consent to the use of at least one medically approved contraceptive (eg intrauterine devices, contraceptives or condoms) is performed during the study treatment period and within 3 months of the end of the study treatment period.
排除标准
- •Patients with cancerous meningitis (ie meningeal metastasis);
- •Patients with active central nervous system (CNS) metastasis.
- •Spinal cord compression that cannot be radically treated with surgery and/or radiotherapy cannot be enrolled.
- •Patients with double cancer or more serious cancer;
- •Patients with a history of autoimmune diseases;
- •Significant clinical significance in the history of cardiovascular disease;
- •Arterial/venous thrombosis events such as cerebrovascular accidents deep vein thrombosis and pulmonary embolism within 6 months prior to first administration;
- •Have a history of immunodeficiency including HIV infection;
- •Active hepatitis B or hepatitis C patients;
- •Any disease or symptom that is not appropriate for inclusion in this study determined by the investigator.;
- •Patients have undergone major surgery within 28 days prior to the first dose (except for diagnostics);
- •Those who used a live attenuated vaccine within 4 weeks prior to the first dose or expect a live attenuated vaccine during the study period;
- •Those who received other clinical trials within 4 weeks prior to the first study;
- •Those who received systemic immunosuppressive therapy within 2 weeks prior to the first study dose;
- •Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation;
- •A history of severe allergic reactions to other monoclonal antibody/fusion protein drugs;
- •Mental illness, alcohol abuse, drug abuse or substance abuse;
- •Any disease or condition that causes reasonable suspicion to prohibit the use of the study drug or affect the interpretation of the study results or the patient is at high risk of treatment complications (any other disease, metabolic disorder, physical examination results or laboratory tests abnormalities);
- •Pregnant or lactating women or women planning to become pregnant during the study.
研究组 & 干预措施
SHR-1501 and SHR-1316 dose escalation
SHR-1501 given subcutaneously with different doses. SHR-1316 given intravenously.
干预措施: SHR-1501 (Drug)
SHR-1501 and SHR-1316 dose escalation
SHR-1501 given subcutaneously with different doses. SHR-1316 given intravenously.
干预措施: SHR-1316 (Drug)
SHR-1501 and SHR-1316 dose expansion
SHR-1501 given subcutaneously with different doses. SHR-1316 given intravenously.
干预措施: SHR-1501 (Drug)
SHR-1501 and SHR-1316 dose expansion
SHR-1501 given subcutaneously with different doses. SHR-1316 given intravenously.
干预措施: SHR-1316 (Drug)
SHR-1501 and SHR-1316 Indication expansion
SHR-1501 given subcutaneously with a recommended dose. SHR-1316 given intravenously.
干预措施: SHR-1501 (Drug)
SHR-1501 and SHR-1316 Indication expansion
SHR-1501 given subcutaneously with a recommended dose. SHR-1316 given intravenously.
干预措施: SHR-1316 (Drug)
结局指标
主要结局
Dose-limiting toxicity and Maximum tolerated dose
时间窗: Approximately 42 Days.
Dose-limiting toxicity and Maximum tolerated dose in patients with advanced tumors treated by SHR-1501 combined with SHR-1316.
Recommended Phase 2 dose (RP2D)
时间窗: Approximately 2 years
Recommended Phase 2 dose (RP2D) based on comprehensive evaluation
Adverse event/Serious adverse event
时间窗: Approximately 2 years
Incidence/severity of adverse events/serious adverse events (rated based on CTC AE v5.0)
次要结局
- Immune related features(Approximately 2 years)
- Objective response rate(Approximately 2 years)
- Disease control rate(Approximately 2 years)
- Pharmacokinetic (PK)(Approximately 2 years)
- 12 months overall survival(Approximately 2 years)
- Immunogenicity(Approximately 2 years)
- Duration of response(Approximately 2 years)
- progression-free survival(Approximately 2 years)
- Durable clinical benefit rate at 6 month(Approximately 2 years)