A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL092 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 140
- 试验地点
- 27
- 主要终点
- Dose-Escalation Stage: MTD/recommended dose for XL092
研究概览
简要总结
This is a Phase 1, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect on biomarkers of XL092 administered alone, in combination with atezolizumab, and in combination with avelumab to subjects with advanced solid tumors.
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 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
XL092 Single-Agent Dose-Escalation Cohorts
Subjects will accrue in cohorts of 3-6 subjects in a standard "3 plus 3" design.
干预措施: XL092 (Drug)
XL092 Single-Agent Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in clear cell renal cell carcinoma (ccRCC), non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), and metastatic castration-resistant prostate cancer (mCRPC).
干预措施: XL092 (Drug)
XL092 + Atezolizumab Dose-Escalation Cohorts
Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.
干预措施: XL092 (Drug)
XL092 + Atezolizumab Dose-Escalation Cohorts
Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.
干预措施: Atezolizumab (Drug)
XL092 + Atezolizumab Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), metastatic castration-resistant prostate cancer (mCRPC), and colorectal cancer (CRC).
干预措施: XL092 (Drug)
XL092 + Atezolizumab Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), metastatic castration-resistant prostate cancer (mCRPC), and colorectal cancer (CRC).
干预措施: Atezolizumab (Drug)
XL092 + Avelumab Dose-Escalation Cohorts
Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.
干预措施: XL092 (Drug)
XL092 + Avelumab Dose-Escalation Cohorts
Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.
干预措施: Avelumab (Drug)
结局指标
主要结局
Dose-Escalation Stage: MTD/recommended dose for XL092
时间窗: Up to 24 months
To determine the maximum tolerated dose (MTD) and/or recommended dose (RD) for further evaluation of XL092 when administered alone and in combination with immune checkpoint inhibitors (ICIs) to subjects with advanced solid tumors
Cohort-Expansion Stage: Objective Response Rate (ORR)
时间窗: Up to 24 months
To evaluate preliminary efficacy of XL092 when administered alone and in combination with ICIs by estimating ORR as assessed by the Investigator per RECIST 1.1
Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS)
时间窗: Up to 24 months
To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with ICIs for specific cohorts by estimating the percentage of subjects with PFS at 6 months (PFS rate) per RECIST 1.1 as assessed by the Investigator (except for the CRC expansion cohort H)
Cohort-Expansion Stage (Cohort H only): Overall Survival (OS)
时间窗: Up to 24 months
To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with atezolizumab for subjects with RAS wild-type CRC (Cohort H Treatment Arms H-A and H-B) by estimating overall survival (OS)
次要结局
- Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)(Up to 24 months)
- Incidence and Severity of Nonserious Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 36 months)
- Dose-Escalation Stage: Terminal Half-Life(Up to 24 months)
- Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)(Up to 24 months)
- Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)(Up to 24 months)
- Dose-Escalation Stage: Apparent Clearance (CL/F)(Up to 24 months)
研究者
Exelixis, Inc.
Scientific
Exelixis Inc.