Phase 1/2a Open-label Clinical Trial Evaluating VBC108, a CLDN18.2 and CDH17-directed Bi-specific Antibody Drug Conjugate, in Participants With Advanced Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 230
- 试验地点
- 24
- 主要终点
- Incidence of dose-limiting toxicities (DLT) as defined in the protocol
研究概览
简要总结
This is a multicenter, open-label, multiple-dose, FIH Phase 1/2a trial. The Phase 1 portion uses Bayesian optimal interval (BOIN) design to escalate and determine the MTD and/or RP2D with potential backfill cohorts. The Phase 2a portion consists of dose optimization followed by cohort expansion to confirm safety and tolerability and to further evaluate the efficacy of the selected RP2D in selected solid tumor malignancies for VBC108.
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
- •The participant or the participant's legally acceptable representative is willing and able to provide a written ICF before initiating any trial procedure.
- •Histologically or cytologically confirmed unresectable advanced/metastatic solid tumor .
- •At least one measurable lesion as assessed by the investigator according to RECIST v1.1 criteria.
- •Male or female adults (defined as ≥ 18 years of age).
- •ECOG performance status 0-
- •Life expectancy greater than 12 weeks.
- •Archived tumor tissue sample available or able to undergo a fresh biopsy collection.
- •Adequate organ and bone marrow function.
- •Participants must meet the minimum washout period requirements before the first dose of investigational drug.
排除标准
- •Any unresolved toxicity of Grade ≥2 from previous anti-cancer treatment.
- •Known or suspected brain metastases, or spinal cord compression.
- •Prior treatment with an ADC targeting CLDN18.2x CDH17 bispecific ADC.
- •Prior treatment with any ADC carrying a topoisomerase I inhibitor (TOP1i) payload.
- •Prior treatment with CLDN18.2 targeting CAR-T.
研究组 & 干预措施
VBC108 Dose Level 4
Phase 1 dose escalation and backfill: VBC108 at Dose Level 4
干预措施: VBC108 (Drug)
VBC108 Dose Level 2
Phase 1 dose escalation and backfill: VBC108 at Dose Level 2
干预措施: VBC108 (Drug)
VBC108 Dose Level 3
Phase 1 dose escalation and backfill: VBC108 at Dose Level 3
干预措施: VBC108 (Drug)
VBC108 Dose Level 5
Phase 1 dose escalation and backfill: VBC108 at Dose Level 5
干预措施: VBC108 (Drug)
VBC108 Dose Level recommended Phase 2 dose (RP2D)
Phase 2a expansion cohort: VBC108 at recommended Phase 2 dose (RP2D) across tumor-specific cohorts
干预措施: VBC108 (Drug)
VBC108 Dose Level 1
Phase 1 dose escalation and backfill: VBC108 at Dose Level 1
干预措施: VBC108 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLT) as defined in the protocol
时间窗: From time of first dose of VBC108 to end of DLT period ( 21 days)
Number of patients with at least 1 dose-limiting toxicity (DLT), which is any toxicity defined as a DLT in the Clinical Study Protocol
Incidence of Serious Adverse Events
时间窗: From time of Informed Consent to 30 days post last dose of VBC108
Number of patients with serious adverse events by system organ class and preferred term
Incidence of Adverse Events (AEs)
时间窗: From time of Informed Consent to 30 days post last dose of VBC108
Number of patients with adverse events by system organ class and preferred term
Objective Response Rate (ORR)
时间窗: From first dose of VBC108 to disease progression or death, up to approximately 2 years
The percentage or number of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST v1.1)
次要结局
未报告次要终点