A Phase Ⅰ/Ⅱa Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of HMPL-A251 in Participants With Advanced or Metastatic HER2-Expressing Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Hutchmed
- 入组人数
- 147
- 试验地点
- 18
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is a first-in-human (FIH), phase Ⅰ/Ⅱa, open-label, multicenter clinical study of HMPL-A251 monotherapy in adult participants with unresectable, advanced or metastatic HER2-expressing solid tumors.
详细描述
- To evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of HMPL-A251 in participants with previously treated HER2+ solid tumors
- To characterize the safety and preliminary efficacy of HMPL-A251 at RDEs to determine recommended dose(s) for phase 2 (RP2D) or phase 3 (RP3D) in participants with selected HER2-expressing 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed unresectable advanced or metastatic disease.
- •Have at least one measurable lesion per RECIST v1.1;
- •Life expectancy ≥ 12 weeks;
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1;
- •Weight ≥ 35 kg;
排除标准
- •An established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus.
- •Use of strong inhibitors of cytochrome P450 3A4 enzyme (CYP3A4), and inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) within 5 elimination half-lives or 2 weeks (whichever is longer) before the first dose of study drug;
- •Toxicity from prior anti-tumor therapy has not recovered to Grade 1 or baseline prior to the first dose of study drug (except alopecia). Participants with chronic Grade 2 toxicities may be eligible after discussion between the investigator and Sponsor Medical Monitor (e.g., Grade 2 chemotherapy-induced neuropathy);
- •Baseline blood amylase or lipase exceeds the normal range and are judged by the investigators to be clinically significant;
- •Spinal cord compression, leptomeningeal disease, or clinically active central nervous system (CNS) metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms;
- •Major surgery within 28 days prior to the first dose of study drug. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to the first dose of study drug(s);
研究组 & 干预措施
Part A(Phase I)
Dose Escalation
干预措施: HMPL-A251 (Drug)
Part B(Phase IIa)
Dose Expansion/Dose Optimization
干预措施: HMPL-A251 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Approximately 12 months
At least three participants will be enrolled in each dose cohort. Bayesian optimal interval design with backfill (BF-BOIN) will be used to guide dose escalation and to determine the MTD of HMPL-A251
Recommended doses for expansion (RDE)
时间窗: Approximately 12 months
The RDE will be selected by evaluating all available data from the following criteria under consideration: Determination of MTD achieved during the dose escalation part; Safety data obtained across all different doses tested; Tolerability data, such as chronic toxicities, discontinuations, or withdrawals for toxicity that occur beyond the DLT period; PK data collected at the time of evaluation; Preliminary efficacy data.
Overview of Treatment-emergent Adverse Events (TEAEs)
时间窗: Approximately 24 months
All TEAEs will be graded according to NCI CTCAE v6.0 and coded using the Medical Dictionary for Regulatory Activities (MedDRA).
Objective Response Rate (ORR)
时间窗: At least 6 weeks post dose of first participant up to approximately 24 months
ORR is defined as the proportion of participants with Best objective response (BOR) of confirmed complete response (CR) or partial response (PR), as per investigator's assessment according to RECIST v1.1.
Recommended doses for phase II or III studies (RP2D or RP3D) of HMPL-A251
时间窗: Approximately 12 months
The RP2D or RP3D will be selected by evaluating all available data from the following criteria under consideration: Determination of MTD achieved during the dose escalation part; Safety data obtained across all different doses tested; Tolerability data; PK data; efficacy data.
次要结局
- Disease control rate (DCR)(Approximately 2 years)
- Duration of response (DoR)(Approximately 2 years)
- Time to response (TTR)(Approximately 2 years)
- Progression-free survival (PFS)(Approximately 2 years)
- Overall survival (OS)(Approximately 2 years)
- Pharmacokinetic Analysis(Cmax)(Each cycle(21-day cycle), From C9, every 4 cycles, Approximately 12 months)
- Pharmacokinetic Analysis(Tmax)(Each cycle(21-day cycle), From C9, every 4 cycles, Approximately 12 months)
- Pharmacokinetic Analysis((AUC)(Each cycle(21-day cycle), From C9, every 4 cycles, Approximately 12 months)
- To evaluate the immunogenicity of HMPL-A251(Each cycle(21-day cycle), From C9, every 4 cycles, Approximately 12 months)