A Phase I Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Clinical Activity of RO7673396 as a Single Agent and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors Harboring RAS Mutation(s)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 405
- 试验地点
- 34
- 主要终点
- Stage I: Number of Participants With Adverse Events (AEs)
研究概览
简要总结
This study aims to evaluate the safety and tolerability of RO7673396 in participants with advanced solid tumors harboring RAS mutation(s). This study consists of two stages: Stage 1 (Dose Escalation) and Stage 2 (Dose Expansion). Stage 1 will define the recommended dose(s) for expansion (RDEs) of RO7673396. Stage 2 will evaluate preliminary anti-tumor activity of the RDE(s) defined in Stage 1 and of other doses of interest for future development in selected solid tumor indications.
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
- •Histologically documented, locally advanced, recurrent, or metastatic incurable solid tumors
- •Participants with measurable disease according to RECIST v1.1 assessed by the investigator
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy ≥12 weeks
- •Adequate hematologic and end-organ function
- •Confirmed presence of the RAS mutation(s)
排除标准
- •Current participant or enrollment in another interventional clinical trial
- •Known hypersensitivity or medical contraindication to any component of RO7673396 formulation
- •Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study treatment absorption
- •Known and untreated, or active central nervous system (CNS) metastases
- •Participants with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal (GI) surgery including gastric resection, a history of inflammatory bowel disease (IBD)
- •Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 4 weeks or five half-lives prior to initiation of study treatment
- •Participants who are on acid-reducing agents and unable to safely discontinue them as required in the study
- •Major surgical procedure within 28 days prior to initiation of study treatment, or incomplete recovery from surgery that would interfere with the determination of safety or efficacy of study treatment, or anticipation of need for a major surgical procedure during the study
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Known clinically significant liver disease
研究组 & 干预措施
Stage I
Participants with advanced solid tumors harboring RAS mutations will receive multiple ascending doses of RO7673396, as per a pre-defined dosing regimen until unacceptable toxicity or disease progression (PD) and/or loss of clinical benefit as determined by the investigator.
干预措施: RO7673396 (Drug)
Stage II
Participants with advanced solid tumors harboring RAS mutations will receive RO7673396 at the dose determined in Stage 1, until unacceptable toxicity or PD and/or loss of clinical benefit as determined by the investigator.
干预措施: RO7673396 (Drug)
结局指标
主要结局
Stage I: Number of Participants With Adverse Events (AEs)
时间窗: Up to approximately 40 months
Stage I: Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: Up to Day 21
Stage II: Objective Response Rate (ORR) as Assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)
时间窗: Up to approximately 40 months
次要结局
- Plasma Concentrations of RO7673396 and its Metabolite(s)(Up to approximately 49 months)
- Stage I: ORR as Assessed by the Investigator per RECIST V1.1(Up to approximately 49 months)
- Stage I and II: Duration of Response (DOR) as Assessed by the Investigator per RECIST V1.1(Up to approximately 49 months)
- Stage I and II: Progression-free Survival (PFS) as Assessed by the Investigator per RECIST V1.1(Up to approximately 49 months)