A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX42 (Anti-EGFR ADC) in Patients With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- The Dose-Limiting Toxicity (DLT) of HLX42 within 21 days after the first Administration
研究概览
简要总结
This study is an open-label first-in-human phase I clinical study to evaluate the safety and tolerability of HLX42.
详细描述
The first stage: This study is an open-label first-in-human phase I clinical study to evaluate the safety and tolerability of HLX42 with escalated doses in the treatment of patients with advanced/metastatic solid tumors. In this study, a 3 + 3 dose escalation method will be adopted, and the patients will be administered with HLX42 at different doses via intravenous infusion. The DLT observation period lasts for 3 weeks after the first administration of HLX42.
The second stage: This is a randimazation, open label, 2 arms, muticentral clinical study, about 30 patients in each arm, the total sample size is about 60. Eligible subjects will be randomized in a 1:1 ratio: Group A: HLX42 2.5 mg/kg; Group B: HLX42 2.0 mg/kg. Stratification: tumor tissue type(adenocarcinoma or squamous carcinoma), EGFR-sensitive mutation status (mutant or wild-type or missing).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •≥ 18 years and ≤ 75 years at the time of signing the ICF, male or female;
- •Patients with histologically or cytologically confirmed advanced/metastatic malignant solid tumors, who are refractory to or intolerable with standard treatment, or for which no standard treatment is available(stage 1); Patients with histologically or cytologically confirmed advanced/metastatic malignant NSCLC, who are refractory to or intolerable with standard treatment, or for which no standard treatment is available(stage 2);
- •At least one measurable lesion as per RECIST 1.1；
- •An ECOG performance status score of 0-1；
- •Life expectancy > 3 months;
- •Adequate organ functions as confirmed by laboratory tests within 7 days prior to the first administration of the investigational product;
- •For patients with hepatocellular carcinoma, Child-Pugh score must be A;
排除标准
- •History of other malignant tumors within 2 years prior to the first administration, except for cured cervical carcinoma in situ or cutaneous basal cell carcinoma;
- •The histopathological type is large cell carcinoma, adenosquamous carcinoma, other types (including but not limited to sarcomatoid carcinoma, lymphoepithelioma-like carcinoma, NUT carcinoma, etc.), or contains neuroendocrine pathological components, etc. (stage 2)；
- •History of (non-infectious) ILD requiring the use of steroids, current ILD, or suspected ILD that cannot be ruled out by imaging at screening;
- •Subjects who are allergic to protein preparations/ monoclonal antibodies/ any component in the formulation of the investigational product;
- •Subjects with known previous serious eye disorders;
- •Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to the first administration of the investigational product;
- •Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases;
- •Patients who have been assessed as unsuitable for inclusion by the investigator, due to brain metastases, spinal cord compression, or cancerous meningitis with clinical symptoms, or uncontrolled brain or spinal cord metastases that have been evidenced;
- •Patients who have received long-term systemic steroids treatment (equivalent to prednisone > 10 mg/day) or immunosuppressive agents of any other forms, which should be discontinued at least 2 weeks prior to the first infusion of the investigational product;
- •Patients who have used potent CYP2D6/CYP3A inhibitors or inducers within 2 weeks prior to the first administration;
- •Patients who have history of immunodeficiency, including HIV infection or other acquired or congenital immunodeficiencies, or history of organ transplantation;
- •Patients with active HBV or HCV infection or HBV/HCV co-infection;
- •Pregnant or lactating women;
- •Subjects who are not suitable for participating in this clinical study due to any clinical or laboratory abnormalities or other reasons as assessed by the investigator.
研究组 & 干预措施
HLX42
Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), until progressive disease (PD) without any clinical benefit, initiation of other anti-tumor therapies, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).
干预措施: HLX42 (Drug)
结局指标
主要结局
The Dose-Limiting Toxicity (DLT) of HLX42 within 21 days after the first Administration
时间窗: From first dose to the end of Cycle 1 (each cycle is 3 weeks).
DLT refers to the AEs that are determined to be related to the investigational product by the investigator, whose severity will affect the escalation of dose level. In this study, the DLT observation period lasts for 21 days after the first administration of HLX42.
The maximum tolerated dose (MTD) of HLX42
时间窗: From first dose to the end of Cycle 1 (each cycle is 3 weeks)
The highest dose level, at which DLT is observed in no more than one of 6 evaluable patients, is defined as MTD of HLX42.
次要结局
- Objective response rate (ORR)(approximately up to 24 months)
- Duration of response (DOR)(approximately up to 24 months.)
- Overall survival (OS)(approximately up to 24 months)
- Progression-free survival (PFS)(up to approximately up to 24 months)
- Cmax(Up to 21 days after the first dose)
- T1/2(Up to 21 days after the first dose)
- Tmax(Up to 21 days after the first dose)
- ADA (anti-drug antibody)(approximately up to 24 months)
- Nab (neutralizing antibody)(approximately up to 24 months)
- Number of subjects experiencing adverse events(Day 1 through 90 days after last dose.)