A Phase I, Open-label, Multicenter Study to Assess Safety, Tolerability, Pharmacokinetic, Efficacy and Preliminary Food Effect of BB3008 Tablet Administered Orally to Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Number of subjects with dose limiting toxicities (DLTs)
研究概览
简要总结
This is a Phase 1 dose escalation study to evaluate the safety, tolerability, pharmacokinetics, efficacy and preliminary food effect of BB3008 as monotherapy in subjects with advanced solid tumors.
详细描述
This first-in-human (FIH) study of BB3008 will evaluate safety, tolerability, pharmacokinetics (PK) efficacy and preliminary food effect of BB3008 in subjects with advanced solid tumors. The primary objective is to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of BB3008 as monotherapy, and to evaluate the safety and tolerability of BB3008. The secondary objectives include the assessments of PK profile, preliminary efficacy, preliminary food effect (FE) and preliminary metabolites identification of BB3008. The exploratory objectives are to explore biomarkers and C-QTcF analysis.
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 78 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fully informed of the study and voluntarily signed the informed consent form (ICF), and willing to follow and have the ability to complete all trial procedures.
- •Subjects with histologically or cytologically confirmed advanced solid tumors who are lacking standard therapy, progressing after adequate standard therapy, or intolerant of standard therapy.
- •ECOG score ≤
- •At least one evaluable or measurable lesion as defined by RECIST v1.
- •Expected survival ≥ 3 months.
- •adequate organ function.
- •Female subjects of childbearing potential must have a negative pregnancy test prior to the first dose and are required to use effective contraception from signing the ICF until 6 months after the last dose of study treatment.
排除标准
- •History of dual-source cancer within 5 years.
- •Presence of known active central nervous system (CNS) and/or leptomeningeal metastases.
- •History of clinically serious cardiovascular and cerebrovascular disease within 6 months.
- •Active infection (including, but not limited to HBV or HCV).
- •Received radical radiotherapy within 12 weeks.
- •Received live virus vaccination within 4 weeks.
研究组 & 干预措施
BB3008 monotherapy
The study is composed of fasted dose cohorts and fed dose cohort. BB3008 will be administered orally daily alone as monotherapy in all cohorts. In the fasted dose cohorts, the subjects will receive once daily of BB3008 monotherapy fasted across approximately 6 ascending dose levels. The starting dose is 80 mg/day. In the fed dose cohort, the subjects will receive once daily of BB3008 monotherapy in a fed condition. The dose selected for fed dose cohort must be deemed safe as assessed by safety monitoring committee (SMC).
干预措施: BB3008 tablet (Drug)
结局指标
主要结局
Number of subjects with dose limiting toxicities (DLTs)
时间窗: Single dose to the end of Cycle 1 (each cycle is 21 days)
To assess the safety and tolerability of BB3008 tablet as monotherapy in subjects with advanced solid tumors and to determine the maximum tolerated dose (MTD) of BB3008 tablet, and to provide a basis for determination of the recommended dose (RP2D) for Phase II clinical trials.
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
时间窗: From screening (Day -28 to Day -1) through up to 12 months or until disease progression
AEs and SAEs will be characterized by type, seriousness, relationship to study treatment, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 5.0) and timing.
次要结局
- Pharmacokinetic Assessments: Time to Peak Concentration (Tmax)(Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days))
- Pharmacokinetic Assessments: Elimination half-life (t½)(Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days))
- Objective response rate (ORR)(From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- Disease control rate (DCR)(From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- Progression-free survival (PFS)(From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- Pharmacokinetic Assessments: Peak Plasma Concentration (Cmax)(Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days))
- Pharmacokinetic Assessments: Area under the plasma concentration-time curve (AUC)(Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days))
- Duration of response (DOR)(From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)