A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Recombinant Fully Human Anti-CD39 Monoclonal Antibody JS019 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Safety Incidence of DLT severity of adverse events (AEs) and serious adverse events (SAEs)and tolerability
研究概览
简要总结
This is a phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of JS019 as monotherapy in patients with advanced malignant solid tumors The study includes JS019 monotherapy dose escalation, dose expansion stages to investigate the safety, tolerability, pharmacokinetics and preliminary anti-tumor efficacy of JS019 as monotherapy.
详细描述
Monotherapy Dose Escalation Stage:
In this stage, the safety and tolerability, PK characteristics, immunogenicity and pharmacodynamics characteristics of JS019 are investigated. Four dosage groups are preset: 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg. The drug is administered intravenously every 3 weeks (Q3W). A treatment cycle is 21 days, with a DLT observation period of 21 days after the initial administration. The incremental dose and dosing interval may be adjusted as necessary during the study based on safety, PK, and other results obtained
Monotherapy Dose Expansion Stage:
According to RP2D of JS019 single drug dose, 3-5 specific tumor types are selected for indication expansion, and about 8-12 patients are enrolled for each indication. Tumor types and additional cases could be selected according to the specific situation in the trial process. It is planned to expand the cohort of lung cancer, pancreatic cancer, sarcoma, hepatocellular carcinoma, cholangiocarcinoma and other solid tumors to explore the efficacy and safety of JS019 single drug. The specific cohort will be adjusted according to the results of previous studies.
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
- •Be able to understand and willing to sign the Informed Consent Form;
- •Male or female aged 18~75 years (included);
- •Patients with pathologically confirmed advanced malignant solid tumors
- •Failed or unsuitable for standard treatment;
- •Eastern Cooperative Oncology Group (ECOG) physical fitness score: 0~1;
- •Expected survival period ≥ 12 weeks;
- •At least one measurable lesion according to criteria RECIST v1.1 ;
排除标准
- •Patients with known hypersensitivity to the components of JS019;
- •Patients who have received the treatment with anti-CD39 antibodies or inhibitors;
- •Patients who participated in other clinical studies within 4 weeks prior to the first administration of JS019, except patients are in the follow-up period of observational (non-interventional) clinical study or interventional study;
- •Patients who have received major surgery within 4 weeks before the first dose or expected to undergo major surgery during the study (as judged by the investigator) or are in the recovery period from surgery;
- •Patients who have received anti-tumor therapy, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, or biological therapy, within 4 weeks or 5 half-lives of the therapy (whichever is shorter) prior to the first dose of JS
- •Patients who have received traditional Chinese medicine or Chinese patent medicine preparations with anti-tumor indications within 2 weeks before the first dose of JS
- •Can accept hormone therapy for non-tumor-related diseases (such as insulin therapy for diabetes and hormone replacement therapy, etc.);
研究组 & 干预措施
Dose Escalation: dose level：0.3mg/kg
Dose Escalation: 0.3mg/kg, IV infusion, every 3 weeks (q3w).
干预措施: JS019 (Biological)
Dose Escalation: dose level：1 mg/kg
Dose Escalation: 1 mg/kg IV infusion, every 3 weeks (q3w).
干预措施: JS019 (Biological)
Dose Escalation: dose level：3 mg/kg
Dose Escalation: 3 mg/kg IV infusion, every 3 weeks (q3w).
干预措施: JS019 (Biological)
Dose Escalation: dose level：10 mg/kg
Dose Escalation: 10 mg/kg IV infusion, every 3 weeks (q3w).
干预措施: JS019 (Biological)
结局指标
主要结局
Safety Incidence of DLT severity of adverse events (AEs) and serious adverse events (SAEs)and tolerability
时间窗: 2 years
Incidence of DLT, incidence and severity of adverse events (AE) and severe adverse events (SAE), clinically significant abnormal laboratory changes and other tests
Maximum Tolerated Dose (MTD) or Optimal Biological Effect Dose (OBD) and Phase II study recommended dose (RP2D)
时间窗: 2 years
The safety, pharmacokinetic and preliminary efficacy data of the comprehensive dose escalation were determined. When MTD/OBD is determined, MTD/OBD is usually used as RP2D.
次要结局
- Duration of response (DOR)(2 years)
- Pharmacodynamics （PD）(2 years)
- Immunogenicity(2 years)
- Disease control rate (DCR)(2 years)
- Pharmacokinetics (PK)(2 years)
- Objective response rate (ORR)(2 years)
- Time to response (TTR)(2 years)
- Progression-free survival (PFS)(2 years)
- Overall survival (OS)(2 years)