A Phase 1 Study of JS014, a Recombinant Fusion Protein of Interleukin-21 and Humanized Anti-human Serum Albumin VHH Antibody as a Single Agent or in Combination With Pembrolizumab in Subjects With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- The numbers of participants with treatment-related adverse events assessed by CTCAE 5.0
研究概览
简要总结
This phase 1, first-in-human study uses a BOIN design to assess the safety and potential efficacy of JS014 at different dose levels as a single agent and in combination with fixed dose of pembrolizumab in subjects with advanced cancer.
详细描述
This study has two parts: 1a and Ib. Ia is a single agent study, and Ib is a combination study, testing the safety of JS014 with 200 mg of pembrolizumab. After being informed about the study and the potential risks, all subjects giving written informed consent will receive at most 4-week screening procedures to ensure the eligibility of the study entry. Once eligible, the subjects will receive JS014 infusion at the designated dose levels once every week until disease progression. In Ia study, only JS014 is given. In Ib study, JS014 will be given once a week with pembrolizumab at 200 mg once every three weeks until disease progression. The subjects will receive safety evaluation, pharmacokinetic and pharmacodynamic studies, as well as efficacy evaluation at regular interval.
The maximum number in each part of the study is 30 subjects. The Ia study will be conducted in Taiwan, and Ib study will be conducted in both Taiwan and the United States.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Older 18 years of age or per local regulation
- •Subjects with advanced cancer or lymphoma who have no standard therapy available, ineligible for standard therapy or unwilling to receive cytotoxic therapy .
- •ECOG PS 0-1
- •A life expectancy longer than three months
- •Adequate organ functions
- •Able to adopt effective contraceptive measures
排除标准
- •Known history of allergies to JS014 or IL-21 or human serum albumin or pembrolizumab (Ib only)
- •Subjects who have received major surgery less than 4 weeks before 1st infusion of JS014
- •Subjects who has a history of immune-related adverse events in prior immunotherapy.
- •Subjects who have received immunosuppressive therapy less than 4 weeks before 1st infusion of JS
- •Subjects who have two or more primary cancers in the past 5 years.
- •Newly diagnosed or symptomatic brain metastases.
- •Subjects who have received prior anti-cancer therapy with residual toxicities greater than grade
- •Subjects who have a history of autoimmune disease in 2 years.
- •Subjects who have active infection, or uncontrollable hypertension, unstable angina, active peptic ulcer, recent acute myocardial infarction, severe congestive heart failure, or unhealed wound.
- •Subjects with active hepatitis B or hepatitis C.
- •Subjects who are pregnant or breast feeding.
- •Subjects who primary immune deficiency.
结局指标
主要结局
The numbers of participants with treatment-related adverse events assessed by CTCAE 5.0
时间窗: 24 months
To determine the percentage of various toxicities assessed by CTCAE at different dose levels alone or in combination with pembrolizumab
Maximum tolerated dose (MTD) of JS014
时间窗: 24 months
To determine the MTD of JS014 alone or in combination with pembrolizumab
Recommended phase-2 dose (RP2D) of JS014
时间窗: 24 months
To determine of the RP2D of JS014 alone or in combination of pembrolizumab
次要结局
- Area under the curve (AUC) of JS014(24 months)
- Maximum concentration (Cmax) of JS014(24 months)
- Time to reach maximum concentration (Tmax) of JS014(24 months)
- Overall response rate (ORR) alone or in combination with pembrolizumab(24 months)
- Duration of response (DoR) alone or in combination with pembrolizumab(24 months)
- Half life (T1/2) of JS014(24 months)
- Titers of anti-JS014 antibody(24 months)
- Clearance of JS014(24 months)
- Volume of distribution (Vd) of JS014(24 months)
- Prevalence of anti-JS014 antibody(24 months)