A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ICP-248 as Monotherapy or in Combination With Anti-CD20 Monoclonal Antibody in Patients With Mature B-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 8
- 主要终点
- DLT
研究概览
简要总结
Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ICP-248 as monotherapy or in combination with anti-CD20 monoclonal antibody in Mature B-cell Malignancies
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Known central nervous system involvement by lymphoma/leukemia.
- •Known or suspected history of Richter's transformation.
- •Prior autologous stem cell transplant (unless ≥ 3 months since transplant); or prior chimeric cell therapy (unless ≥ 3 months since cell infusion).
- •A history of allogeneic stem cell transplantation.
- •An interval of less than 5 half-lives from the last dose of a strong CYP3A or CYP2C8 inhibitor or inducer (chemical agent, herbal medicine and dietary supplement) to the first dose of the investigational product, or a plan to use concurrently medications, dietary supplements or food (e.g., grapefruit or grapefruit juice) with strong CYP3A or CYP2C8 inhibitory or inductive effect during study participation
- •Presence of active infection that currently requires intravenous systemic anti-infective therapy.
- •History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
- •History of significant cardiovascular disease
- •Patients with previous or concomitant central nervous system disorders
- •Grade 2 or above toxicity due to prior anti-cancer therapy at screening
- •Known alcohol or drug dependence
- •Unable to swallow tablets or presence of disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
研究组 & 干预措施
Dose-Escalation Cohort - CLL/SLL and MCL
Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose. Cycles will comprise 28 days.
干预措施: ICP-248 (Drug)
Dose-Expansion Cohort A - CLL/SLL
Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose and obinutuzumab for 6 cycles. Cycles will comprise 28 days.
干预措施: ICP-248 (Drug)
Dose-Expansion Cohort A - CLL/SLL
Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose and obinutuzumab for 6 cycles. Cycles will comprise 28 days.
干预措施: Obinutuzumab (G) (Drug)
Dose-Expansion Cohort B - MCL
Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose. Cycles will comprise 28 days.
干预措施: ICP-248 (Drug)
Dose-Expansion Cohort C - MCL
Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose and Rituximab for 18 cycles. Cycles will comprise 28 days.
干预措施: ICP-248 (Drug)
Dose-Expansion Cohort C - MCL
Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose and Rituximab for 18 cycles. Cycles will comprise 28 days.
干预措施: Rituximab (R) (Drug)
结局指标
主要结局
DLT
时间窗: 49 days
Dose-limiting toxicity (DLT) rate at each dose level DLT will be assessed via CTCAE version 5.0 or iwCLL 2018.
Safety and tolerability of ICP-248 at different doses in B-cell malignancies
时间窗: 5 years
To investigate the incidence, nature and severity of adverse events (AE) according to NCI-CTCAE V5.0 evaluation criteria or iwCLL 2018.
次要结局
- Ctrough, ss of ICP-248(Predose up to week 28)
- Cmax, ss of ICP-248(Predose up to week 28)
- Preliminary efficacy of ICP-248 monotherapy in patients with B-cell malignancy(5 years)