A Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability, and Pharmacokinetics/ Pharmacodynamics of APR003 in Patients With Advanced Colorectal Cancer (CRC) With Malignant Liver Lesions
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 4
- 主要终点
- Determine the Number of Patients With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
A Phase 1 dose escalation study to evaluate APR003 in patients with advanced colorectal cancer (CRC) with malignant liver lesions
详细描述
APR003 is a small molecule TLR7 agonist that concentrates in the GI, and liver with limited systemic exposure. It is designed to increase the therapeutic window of a TLR7 agonist by minimizing the side-effects associated with generalized systemic immune activation and inflammation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG performance status of 0 or 1
- •Must have disease that is considered non-surgically resectable.
- •Relapsed or persistent/refractory to at least two prior systemic treatment regimens for locally advanced or metastatic disease considered to be standard-of-care (SOC).
- •Must have previously received an irinotecan or oxaliplatin-based therapy, as well as a targeted antibody therapy for metastatic disease
- •Tumors that are MSI-H/dMMR must have previously received checkpoint inhibitor therapy
- •Adequate hepatic function
- •Adequate renal function
- •Normal coagulation panel
- •Willingness to use effective contraception
排除标准
- •Current or history of CNS metastases
- •Significant cardiovascular disease
- •Pregnant or breastfeeding
研究组 & 干预措施
APR003 Dose Escalation
This portion of the study will evaluate the safety and pharmacokinetics of a range of APR003 doses administered once a week for 21 days in subjects with advance colorectal cancer (CRC) with metastases to the liver and to determine the RP2D.
干预措施: APR003 (Drug)
结局指标
主要结局
Determine the Number of Patients With Dose Limiting Toxicities (DLTs)
时间窗: Until disease progression, or up to approximately 15 months and 18 days, whichever is first
Determine the number of patients who have experienced a Dose Limiting Toxicities (DLT) evaluated by the investigator based on CTCAE Severity Grade.
AUC Over the Dosing Interval (AUClast) of APR003
时间窗: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Maximum Concentration (Cmax) of APR003
时间窗: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Time-to-maximum Concentration (Tmax) of APR003
时间窗: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Area Under the Curve (AUC) From Time Zero to 24 hr (AUC0-24) of APR003
时间窗: Cycle 1 Day 1, Cycle 1 Day 15 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Apparent Total Plasma Clearance (CL/F) of APR003
时间窗: Cycle 1 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
AUC From Time Zero to Time Infinity (AUC0-ꝏ) of APR003
时间窗: Cycle 1 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Elimination Half-life (T1/2) of APR003
时间窗: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Apparent Volume of Distribution at Steady State After Administration (Vss/F) of APR003
时间窗: Cycle 1 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
次要结局
- Objective Response Rate(Until disease progression, or up to approximately 15 months and 18 days, whichever is first)