A Phase 1/2 Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 69
- 试验地点
- 5
- 主要终点
- Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a first-in-human, Phase 1/2 open-label, multicenter, dose-escalation, safety, pharmacokinetics (PK), and biomarker study of CBX-12 in subjects with advanced or metastatic refractory solid tumors.
详细描述
Phase 1 is the dose-escalation portion of the study in which the safety and tolerability of three dosing schedules of CBX-12 will be evaluated. Subjects in Part A will be treated with CBX-12 on a daily x 5 every 3 weeks schedule (treatment in Part A was discontinued in October 2021). Subjects in Phase 1 Part B will be treated with CBX-12 on a daily x 3 every 3 weeks schedule. Subjects in Phase 1 Part C will be treated with CBX-12 once weekly. Subjects in Phase 1 Modified Part B will be treated with CBX-12 once every 3 weeks.
For all parts in Phase 1, after all subjects in a cohort have completed treatment through the DLT period or discontinued treatment due to a DLT, the SRC, composed of the Investigators who have enrolled subjects in the current cohort(s), the study Medical Monitor and ad hoc members (e.g., other Investigators, a statistician) as needed, will review all available safety data, including DLTs and all available PK data for that cohort and make dose-level recommendations.
Once the recommended phase 2 dose (RP2D) has been established in Part B, Part C and Modified Part B, Phase 2 expansion cohorts may open.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has a histologically- or cytologically-diagnosed solid tumor which is advanced or metastatic and which has progressed on or following at least one systemic therapy regimen administered for advanced or metastatic disease or for which no approved therapy exists. Subject's prior treatment should include all approved regimens that have demonstrated a survival advantage for the subject's disease, stage, and line of therapy.
- •Has measurable disease per RECIST 1.
- •An adequate tumor sample must be available from core needle biopsies obtained during the Screening Period and following the subject's most recent systemic therapy.
- •Agrees to an on-treatment biopsy preferably of the same lesion from which the pre-CBX-12 treatment sample was obtained as long as the Investigator determines such biopsy can be performed with acceptable safety. (Removed Amd 4, date 31-Mar-2023)
排除标准
- •Cytotoxic chemotherapy, biologic agent, investigational agent, or radiation therapy less than or equal to 3 weeks prior to the first dose of CBX-
- •The interval may be reduced to 2 weeks for bone only radiation therapy or investigational agents not expected to be associated with adverse events (AEs) after 2 weeks of last administration, with Medical Monitor approval.
- •Small-molecule kinase inhibitors or hormonal agents less than or equal to 14 days prior to the first dose of CBX-
- •Subjects who are currently receiving any other anti cancer or investigational agent(s).
- •Clinically significant intercurrent disease.
- •Subjects with primary central nervous system (CNS) tumors or clinically active CNS metastases or carcinomatous meningitis. Subjects with stable brain metastasis may be enrolled with Medical Monitor approval.
研究组 & 干预措施
Phase 1 Schedule B Dose Escalation (Daily Dosing x 3)
CBX-12 administered on a daily x 3, 3 week schedule
干预措施: CBX-12 (Drug)
Phase 1 Schedule A Dose Escalation (Daily Dosing x 5)
CBX-12 administered on a daily x 5, 3 week schedule
干预措施: CBX-12 (Drug)
Phase 2 Metastatic Breast Expansion Cohort
CBX-12 administered TBD
干预措施: CBX-12 (Drug)
Phase 1 Modified Schedule B Dose Escalation (Once Every 3 weeks)
CBX-12 administered once every 3 weeks
干预措施: CBX-12 (Drug)
Phase 1 Schedule C Dose Escalation (Once Weekly Dosing )
CBX-12 administered once weekly, 4 week schedule
干预措施: CBX-12 (Drug)
Phase 2 Ovarian Cancer Expansion Cohort
CBX-12 administered TBD
干预措施: CBX-12 (Drug)
结局指标
主要结局
Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Through the end of study, estimated as 6 months
NCI CTCAE v5.0
Phase 1: Recommended Phase 2 Dose for Daily x 3 every 3 weeks schedule of CBX-12 (Schedule B)
时间窗: 15 months
Safety Review Committee Analysis of Safety and PK Data
Phase 1: Recommended Phase 2 Dose for Once Every 3 Weeks schedule of CBX-12 (Modified Schedule B)
时间窗: 15 months
Safety Review Committee Analysis of Safety and PK Data
Phase 1: Recommended Phase 2 Dose for Once Weekly schedule of CBX-12 (Schedule C)
时间窗: 15 months
Safety Review Committee Analysis of Safety and PK Data
Phase 2: Overall response rate (ORR)
时间窗: Through the end of study, estimated as 6 months
ORR Based on RECIST v1.1
次要结局
- Area under the curve from 0-24 hours of CBX-12(5 days)
- Time to maximum concentration of CBX-12(5 days)
- Half-life of CBX-12(5 days)
- Clearance (CL) of CBX-12(5 days)
- Maximum concentration of CBX-12(5 days)
- Progression-free Survival (PFS)(Through the end of study, estimated as 6 months)
- Apparent Volume of Distribution at Steady State (Vss) CBX-12(5 days)
- Phase 1: ORR(Through the end of study, estimated as 6 months)
- Duration of Response (DoR)(Through the end of study, estimated as 6 months)
- Phase 2: Incidence of TEAEs(Through the end of study, estimated as 6 months)