A Phase 1, Open-Label, First-in-Human, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MT-303 in Adults With Advanced or Metastatic GPC3-Expressing Cancers, Including Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 9
- 主要终点
- Change from baseline in ECG parameters
研究概览
简要总结
This is a multicenter, open-label, Phase 1, first-in-human, dose-escalation study designed to assess the safety, tolerability and define the RP2D of MT-303 alone (Module 1) and in combination with Atezo/Bev (Module 2) in participants with advanced hepatocellular carcinoma expressing GPC3.
详细描述
Participants will be enrolled into one of two treatment modules:
- Module 1 (Monotherapy): Participants will receive MT-303.
- Module 2 (Combination therapy): Participants will receive MT-303 in combination with atezolizumab + bevacizumab (Atezo/Bev).
In Module 1 (Monotherapy), participants will receive MT-303 across five dose-escalation cohorts and in Module 2 (Combination therapy), participants will receive MT-303 in combination with Atezo/Bev across five dose-escalation cohorts.
Additional cohorts in both modules may be scheduled based on emerging safety and PK data.
Participants will be sequentially enrolled into Cohorts 1 through 5. Both modules will be enrolled concurrently, with Module 2 dosing beginning at one dose level below the known safe dose in Module 1. Safety Review Committee decisions will be informed by all available safety data from Modules 1 and 2.
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
- 未提供
排除标准
- •Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- •Significant cardiovascular disease
- •History of severe hypersensitivity to atezolizumab and/or bevacizumab.
- •History of idiopathic pulmonary fibrosis
- •Prior history of hypertensive crisis or hypertensive encephalopathy.
研究组 & 干预措施
MT-303
Participants will receive MT-303 through intravenous infusion.
干预措施: MT-303 (Drug)
MT-303 + Atezolizumab + Bevacizumab
Participants will receive MT-303 in combination with Atezo/Bev through intravenous infusion.
干预措施: MT-303 +Atezolizumab + Bevacizumab (Drug)
结局指标
主要结局
Change from baseline in ECG parameters
时间窗: Screening, Day 1 and Day 15
Type, incidence and severity of Adverse Events
时间窗: Up to 2 years from the last dose of Investigational Medicinal Product (IMP)
Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0
Recommended Phase 2 Dose (RP2D)
时间窗: 28 days from the last dose of IMP
The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data
Optimal Biological dose (OBD)
时间窗: 21 days from the last dose of IMP
The OBD will be determined using dose limiting toxicities (DLTs) and all other available study data
Change from baseline in vital signs
时间窗: Up to 30 days from the last dose of IMP
Temperature, weight, height, pulse rate and blood pressure will be assessed
Change in laboratory parameters
时间窗: Up to 30 days from the last dose of IMP
Hematology, chemistry, coagulation, virology and urine analysis will be assessed.
次要结局
- To assess adverse events of special interest (AESI) by measuring infusion reaction(upto 2 years from the last dose of IMP)
- To assess adverse events of special interest (AESI) by measuring hypersensitivity reaction(Up to 2 years from the last dose of IMP)
- To assess adverse events of special interest (AESI) by measuring cytokine release syndrome (CRS)(Up to 2 years from the last dose of IMP)
- Pharmacokinetics (PK)(Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.)
- To assess adverse events of special interest (AESI) by checking for second primary malignancy(upto 2 years from the last dose of IMP)
- To assess adverse events of special interest (AESI) by measuring immune effector cell-associated neurotoxicity syndrome (ICANS)(Up to 2 years from the last dose of IMP)