A Phase 1, Multicenter, Open-Label, First-in-Human Study of the Safety and Pharmacokinetics of VIR-5818 Alone and in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 645
- 试验地点
- 22
- 主要终点
- Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)- Parts 1, 2, 3, and 4
研究概览
简要总结
This first-in-human (FIH) Phase 1 open-label multicenter dose-escalation and dose-expansion study is designed to evaluate the safety, pharmacokinetics, and preliminary activity of VIR-5818 (Formerly AMX-818) as a single agent and in combination with pembrolizumab in participants with HER2+ tumors across multiple tumor types. The study will be conducted in four parts:
- Part 1 (dose escalation): Single-agent VIR-5818
- Part 2 (dose escalation): VIR-5818 plus pembrolizumab
- Part 3 (dose expansion): Single-agent VIR-5818
- Part 4 (dose expansion): VIR-5818 plus pembrolizumab
The total length of the study, from screening of the first participant to the end of the study, is expected to be approximately 72 months.
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
- •Written informed consent by the participant (or legally acceptable representative if applicable)
- •Life expectancy of at least 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Diseases under study, prior lines of therapy, and human epidermal growth factor receptor 2 (HER2) status, per local tests
排除标准
- •Significant cardiopulmonary disease and recent cardiac events
- •History of major organ autoimmune diseases
- •Acute or chronic infections
- •The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
研究组 & 干预措施
Part 4 (dose expansion
Participants will receive VIR-5818 plus pembrolizumab
干预措施: VIR-5818 (Drug)
Part 4 (dose expansion
Participants will receive VIR-5818 plus pembrolizumab
干预措施: pembrolizumab (Drug)
Part 2 (dose escalation)
Participants will receive VIR-5818 plus pembrolizumab
干预措施: pembrolizumab (Drug)
Part 1 (dose escalation)
Participants will receive single-agent VIR-5818
干预措施: VIR-5818 (Drug)
Part 2 (dose escalation)
Participants will receive VIR-5818 plus pembrolizumab
干预措施: VIR-5818 (Drug)
Part 3 (dose expansion)
Participants will receive single-agent VIR-5818
干预措施: VIR-5818 (Drug)
结局指标
主要结局
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)- Parts 1, 2, 3, and 4
时间窗: Up to approximately 55 months
Incidence of dose-limiting toxicity - Part 1 and Part 2
时间窗: Up to approximately 21 days (Part 1) and 42 days (Part 2)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)- Parts 1, 2, 3, and 4
时间窗: Up to approximately 55 months
Objective Response Rate (ORR) - Part 3 and Part 4
时间窗: Up to approximately 55 months
ORR defined as a Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
Duration of Response (DOR) - Part 3 and Part 4
时间窗: Up to approximately 55 months
DOR defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST v.1.1.
次要结局
- Pharmacokinetics (PK) parameter: Area under the concentration-time curve (AUC)(Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months)
- DOR - Part 3 and Part 4(Up to approximately 55 months)
- ORR - Part 3 and Part 4(Up to approximately 55 months)
- PK parameter: Maximum plasma concentration (Cmax)(Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months)
- PK parameter: Minimum serum concentration (Cmin)(Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months)
- PK parameter: Clearance (CL)(Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months)
- PK parameter: Volume of distribution at steady-state (Vss)(Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months)
- PK parameter: Accumulation ratio(Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months)
- PK parameter: Half-life (t1/2)(Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months)
- Incidence of anti-drug antibodies (ADAs) to VIR-5818(Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 55 months)
- All parts: Disease control rate (DCR)(Up to approximately 55 months)