An Open-Label, Multicenter, Dose-Escalation and Expansion, Phase I Study to Evaluate Safety, Pharmacokinetics, And Anti-Tumor Activity of RO7300490, A Fibroblast Activation Protein-α (FAP) Targeted CD40 Agonist, as Single Agent or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 11
- 主要终点
- Objective Response Rate (ORR) (Part 3)
研究概览
简要总结
A study to evaluate the safety, pharmacokinetics and anti-tumor activity of RO7300490 as a single agent or in combination with atezolizumab. The study will consist of 3 parts: [Part 1] Dose-Escalation of RO7300490 as a single agent; [Part 2] Dose-Escalation of RO7300490 in combination with atezolizumab and [Part 3] Dose-Expansion of RO7300490 in combination with atezolizumab in selected cancer types.
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
- •Life expectancy of >= 12 weeks.
- •Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors that are not amenable to standard therapy.
- •Radiologically measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Agreement to provide protocol-specific biopsy material.
- •Adverse Events (AEs) from prior anti-cancer therapy resolved to Grade =<
- •Adequate performance status and cardiovascular, hematological, liver, renal and coagulation function.
- •For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating eggs.
- •For male participants: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm.
排除标准
- •Known central nervous system (CNS) primary tumors or metastases, including leptomeningeal metastases, unless protocol-specific conditions are met.
- •Active second invasive malignancy within two years prior to screening.
- •Significant cardiovascular/cerebrovascular disease within 6 months prior to study treatment start.
- •Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.
- •Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
- •Active or history of autoimmune disease.
- •Known hypersensitivity to any of the components of RO7300490 formulation or to components of atezolizumab formulation.
- •Pregnancy, lactation or breastfeeding.
- •Dementia or altered mental status that would prohibit informed consent.
- •Major surgery or significant traumatic injury within 28 days prior to the first study drug administration (excluding biopsies) or anticipation of the need for major surgery during study treatment.
- •Treatment with radiotherapy, chemotherapy, hormonal therapy, targeted therapy, immunotherapy or investigational drug concurrent or within 28 days or 5 half-lives of the drug (whichever is shorter) before the first study drug administration.
研究组 & 干预措施
Part 1: Dose Escalation (RO7300490 Monotherapy)
Participants will receive escalating doses of RO7300490 intravenously (IV) as a single agent for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.
干预措施: RO7300490 (Drug)
Part 2: Dose Escalation (RO7300490/atezolizumab combination therapy)
Participants will receive escalating doses of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label) for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.
干预措施: RO7300490 (Drug)
Part 2: Dose Escalation (RO7300490/atezolizumab combination therapy)
Participants will receive escalating doses of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label) for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.
干预措施: Atezolizumab (Drug)
Part 3: Dose Expansion (Disease-specific Expansion(s))
Participants with selected types of advanced and/or metastatic tumors will receive the maximum tolerated dose (MTD) or recommended dose for expansion (RDE) (determined from Parts 1 and 2) of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label). Treatment will be administered for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.
干预措施: RO7300490 (Drug)
Part 3: Dose Expansion (Disease-specific Expansion(s))
Participants with selected types of advanced and/or metastatic tumors will receive the maximum tolerated dose (MTD) or recommended dose for expansion (RDE) (determined from Parts 1 and 2) of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label). Treatment will be administered for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR) (Part 3)
时间窗: Up to 48 months
Percentage of Participants with Adverse Events (AEs) (Parts 1 and 2)
时间窗: Up to 36 months
Percentage of Participants with Dose-Limiting Toxicities (DLTs) (Parts 1 and 2)
时间窗: Up to 36 months
次要结局
- Area Under The Curve (AUC) of RO7300490 (Parts 1, 2 and 3)(Up to 48 months)
- Clearance (CL) of RO7300490 (Parts 1, 2 and 3)(Up to 48 months)
- Volume of Distribution at Steady State (Vss) of RO7300490 (Parts 1, 2 and 3)(Up to 48 months)
- Percentage of Participants With Adverse Events (AEs) (Part 3)(Up to 48 months)
- Minimum Concentration (Cmin) of RO7300490 (Parts 1, 2 and 3)(Up to 48 months)
- Maximum Concentration (Cmax) of RO7300490 (Parts 1, 2 and 3)(Up to 48 months)
- Percentage of Participants with Anti-RO7300490 Antibodies (Parts 1, 2 and 3)(Up to 48 months)
- Objective Response Rate (ORR) (Parts 1 and 2)(Up to 48 months)
- Disease Control Rate (DCR) (Parts 1, 2 and 3)(Up to 48 months)
- Duration of Response (DOR) (Parts 1, 2 and 3)(Up to 48 months)
- Progression-Free Survival (PFS) On-Treatment (Parts 1, 2 and 3)(Up to 48 months)