A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics and Initial Efficacy of HLX35 (Recombinant Human Anti-EGFR and Anti-4-1BB Bispecific Antibody) in Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 82
- 试验地点
- 2
- 主要终点
- The proportion of patients experiencing dose limiting toxicity (DLT) events
研究概览
简要总结
This Phase1, multicenter, first-in-human, open-label, dose-escalation, and dose expansion study will evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor efficacy of HLX35 administered as a single-agent by IV infusion every 2 weeks to patients with locally advanced or metastatic solid malignancies, who have failed or are intolerant to standard therapy, or for whom no standard therapy is available. This study has two parts: phase 1a dose escalation and phase 1b dose expansion.
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
- •Volunteer to participate in this clinical study; completely understand and know this study as well as sign the informed consent form (ICF);
- •Age ≥ 18 years;
- •Phase 1a dose escalation: patients must have histologically or cytologically confirmed malignant solid tumors which are advanced or metastatic, have failed prior standard treatment, and be intolerant or ineligible for standard therapy;
- •Phase 1b dose expansion: patients must have a histological or cytological diagnosis of Squamous Non-Small Cell Lung Cancer (EGFR H score ≥200 confirmed by central lab) which is advanced or metastatic, have failed prior standard treatment, and be intolerant or ineligible for standard therapy;
- •Measurable disease according to RECIST Version 1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
- •Expected survival 12 weeks;
- •Adequate organ function;
排除标准
- •Systemic anti-cancer treatment or investigational agents in the 28 days prior to the first study dosing;
- •Patients who still have persistent ≥ grade 2 toxicities from prior therapies;
- •Active CNS metastasis;
- •History of any secondary malignancy in the past 5 years;
- •Active autoimmune disease;
- •Human immunodeficiency virus (HIV) infection;
研究组 & 干预措施
Phase 1a dose-escalation stage
Phase 1a uses the "3+3" design, to investigate the safety and determine the MTD of HLX35. Seven dose levels of 0.015 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg are planned for dose finding. Enrollment will continue until a maximum of 42 patients are enrolled
干预措施: HLX35 (Drug)
Phase 1b dose-expansion stage
Patients with sqNSCLC (EGFR H score≥200) will be enrolled in two expansion cohorts, at doses equal to or lower than the MTD, to better characterize the safety, tolerability, PK variability, and preliminary efficacy of single-agent HLX35. Phase 1b dose expansion will include 15-20 per-protocol treated patients, as defined above, in each of the two expansion cohorts.
干预措施: HLX35 (Drug)
结局指标
主要结局
The proportion of patients experiencing dose limiting toxicity (DLT) events
时间窗: from first dose to the end of Cycle 2 (each cycle is 14 days)
Recommended phase 2 dose (RP2D)
时间窗: from first dose to the end of Cycle 2 (each cycle is 14 days)
Incidence of Treatment-Related Adverse Events
时间窗: 2 years
The maximum tolerated dose (MTD)
时间窗: from first dose to the end of Cycle 2 (each cycle is 14 days)
次要结局
- Clearance (CL) of HLX35(2 years)
- Peak plasma concentration (Cmax) of HLX35(2 years)
- Elimination half-life (t1/2) of HLX35(2 years)
- Volume of distribution (Vz) of HLX35(2 years)
- Accumulation Index (Rac) of HLX35(2 years)
- 4-1BB receptor occupancy on circulating T cells(2 years)
- Time to peak (Tmax) of HLX35(2 years)
- Area under the concentration-time curve (AUC) of HLX35(2 years)
- The level of 4-1BB in serum(2 years)
- Duration of response (DOR)(2 years)
- Incidence of treatment-emergent anti-drug antibodies (ADA)(2 years)
- Objective response rate (ORR)(2 years)
- Disease control rate (DCR)(2 years)