A Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HDM2017 Combination Therapy in Participants With Advanced Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is a multicenter, open-label, dose-escalation/dose-expansion, Phase Ib/II study to evaluate the safety, tolerability, PK characteristics, and preliminary anti-tumor efficacy of HDM2017 combination therapy in participants with advanced CRC. The study is divided into two periods: dose escalation (Phase Ib) and dose expansion (Phase II). Phase Ib of this study is a dose-finding study of different HDM2017 combination therapies. The Phase II study will be conducted at a dose determined to be safe and potentially effective in Phase Ib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Participants must voluntarily participate in this study and sign the written ICF after being fully informed.
- •Male or female participants aged 18 to 75 years (inclusive).
- •Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic CRC.
- •Able to provide fresh or archived tumor tissue samples during the screening period.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or
- •Life expectancy ≥ 3 months.
- •Participants must have at least one measurable lesion according to RECIST v1.
- •Laboratory test results at the screening period must indicate that the participant has adequate organ function.
- •Women of childbearing potential (WOCBP) must agree to use a reasonable method of contraception from the time of signing the ICF until 7 months after the last dose; and must have a negative serum human chorionic gonadotropin (HCG) test within 7 days before the first dose. Male participants must agree to use adequate contraception from the first dose until 7 months after the last dose.
- •Participants must be willing and able to complete regular visits, treatment plans, laboratory tests, and other study procedures.
排除标准
- •Prior or current treatment with topoisomerase I (TOP I) inhibitor drugs.
- •Prior or current treatment targeting CDH
- •Presence of other malignant tumor, other than the tumor being treated in this study.
- •AEs from prior therapy that have not resolved to Grade 1 or baseline status before prior therapy.
- •Active central nervous system (CNS) metastasis; metastases to meninges or brainstem metastasis; presence of spinal cord compression.
- •Presence of diseases that may affect the efficacy and safety of the IMP.
- •Known or suspected allergic reaction or contraindication to any component of the IMP or its analogues.
- •Pregnant or lactating women, or those who plan to become pregnant during the study.
研究组 & 干预措施
HDM2017 + bevacizumab + leucovorin + fluorouracil
干预措施: Leucovorin (Drug)
HDM2017 + bevacizumab + oxaliplatin + leucovorin + fluorouracil
干预措施: HDM2017 (Drug)
HDM2017 + bevacizumab + leucovorin + fluorouracil
干预措施: HDM2017 (Drug)
HDM2017 + bevacizumab + oxaliplatin + capecitabine
干预措施: HDM2017 (Drug)
HDM2017 + bevacizumab + oxaliplatin + capecitabine
干预措施: Oxaliplatin (Drug)
HDM2017 + bevacizumab + oxaliplatin + capecitabine
干预措施: Capecitabine (Drug)
HDM2017 + bevacizumab + oxaliplatin + leucovorin + fluorouracil
干预措施: Leucovorin (Drug)
HDM2017 + bevacizumab + leucovorin + fluorouracil
干预措施: Bevacizumab (Drug)
HDM2017 + bevacizumab + oxaliplatin + leucovorin + fluorouracil
干预措施: Bevacizumab (Drug)
HDM2017 + bevacizumab + oxaliplatin + leucovorin + fluorouracil
干预措施: Oxaliplatin (Drug)
HDM2017 + bevacizumab + oxaliplatin + leucovorin + fluorouracil
干预措施: Fluorouracil (Drug)
HDM2017 + bevacizumab + leucovorin + fluorouracil
干预措施: Fluorouracil (Drug)
HDM2017 + bevacizumab + oxaliplatin + capecitabine
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 30 days after the last dose of IMP
The MTD will be determined using DLTs
Recommended Phase 2 Dose (RP2D)
时间窗: 30 days after the last dose of IMP
The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data
Type, incidence and severity of Adverse Events
时间窗: 30 days after the last dose of IMP
Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v6.0
Objective Response Rate (ORR)
时间窗: From date of first-dosing until the date of first documented progression or date of 30 days after the last dose of IMP, whichever came first, assessed up to about 12 months
ORR is defined as the proportion of subjects with BOR response of CR or PR (based on RECIST Version 1.1).
次要结局
- Disease control rate (DCR)(30 days after the last dose of IMP)
- Duration of Response (DoR)(From date of confirm ORR until the date of first documented progression, assessed up to about 36 months)
- Progression Free Survival (PFS)(From date of first-dosing/randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to about 36 months)
- Overall survival (OS)(From date of first-dosing/randomization until the end of the trail or date of death from any cause, whichever came first, assessed up to about 48 months)
- Incidence of anti-drug antibody (ADA)(30 days after the last dose of IMP)