A Phase I Clinical Trial to Investigate the Pharmacokinetics, Safety, and Tolerability of HS-20117-2 Injection in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Evaluation of PK parameters of HS-20117: Cmax
研究概览
简要总结
This trial is a multicenter, open-label, Phase I clinical study designed to evaluate the pharmacokinetics, safety, and tolerability of HS-20117-2 in patients with advanced solid tumors.
详细描述
This trial is a multicenter, open-label, Phase I clinical study designed to evaluate the pharmacokinetics, safety, and tolerability of HS-20117-2 in patients with advanced solid tumors. The study aims to characterize the pharmacokinetic of HS-20117-2 following subcutaneous administration and to identify a dose level that achieves PK exposure comparable to that of the recommended intravenous HS-20117 dosing regimen. By integrating the safety and tolerability data of HS-20117-2 at this dose level, the study will provide a rationale for dose selection in subsequent pivotal clinical trials of HS-20117-2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Aged 18 to 75 years, male or female.
- •According to RECIST v1.1, the investigator assesses that the participant has at least one target lesion.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 1, with no deterioration within 2 weeks prior to the first dose.
- •Minimum life expectancy greater than 12 weeks.
- •Female patients of childbearing potential, from signing the informed consent until 6 months after the last dose, are willing to adopt appropriate contraceptive measures and should not be breastfeeding; male patients, from signing the informed consent until 6 months after the last dose, are willing to use barrier contraception (i.e., condoms).
- •Female patients must have a negative blood pregnancy test result within 7 days prior to the first dose, or demonstrate no risk of pregnancy.
- •Voluntarily participate in this clinical trial, understand the study procedures, and be capable of providing written informed consent.
排除标准
- •Presence of prior anti-tumor therapy-related toxicities with a severity ≥ Grade 2 (according to CTCAE v5.0), excluding alopecia and neurotoxicity.
- •Meeting any of the following cardiac criteria:
- •Mean QT interval corrected by Fridericia's formula (QTcF) > 470 msec on resting ECG.
- •Resting ECG abnormalities indicating clinically significant rhythm, conduction, or morphological abnormalities as judged by the investigator (e.g., complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval > 250 msec).
- •Presence of any factor that increases the risk of QT prolongation or arrhythmic events judged by the investigator as clinically significant (e.g., heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death in a first-degree relative under 40 years of age, or any concomitant medication known to prolong the QT interval).
- •Left ventricular ejection fraction (LVEF) < 50%.
- •Presence of severe, uncontrolled, or active cardiovascular or cerebrovascular diseases.
- •Severe or poorly controlled hyperglycemia.
- •Severe or poorly controlled hypertension.
- •Clinically significant bleeding symptoms or obvious bleeding tendency within 1 month prior to the first dose of study treatment.
- •History of severe arterial or venous thrombotic events within 3 months prior to the first dose of study treatment.
- •Ongoing or active infection within 4 weeks prior to the first dose of study treatment.
- •Current or anticipated requirement for long-term (≥ 30 days) systemic corticosteroid therapy (>10 mg/day prednisone or equivalent) within 30 days prior to enrollment, except for patients requiring chronic inhaled corticosteroids for asthma or topical corticosteroid use. History of immunodeficiency, other acquired or congenital immunodeficiency diseases, or history of organ transplant or allogeneic bone marrow transplantation (excluding corneal transplant).
- •Presence of active infectious diseases.
- •History of hepatic encephalopathy, hepatorenal syndrome, or cirrhosis ≥ Child-Pugh class B.
- •Presence of interstitial lung disease (ILD). Evidence of active pneumonia on chest imaging during screening. Patients requiring long-term continuous oxygen therapy.
- •Severe neurological or psychiatric disorders that may interfere with study evaluation.
- •Female patients who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study or within 6 months after the last dose of the investigational product.
- •History of severe allergies, or known hypersensitivity to any component of HS-20117 or drugs in the same class as HS-
- •Patients judged by the investigator as likely to have poor compliance with the study procedures and requirements.
- •Any condition that, in the investigator's judgment, jeopardizes patient safety or interferes with the study evaluation.
研究组 & 干预措施
HS-20117-2 Injection Q2W Dosing Regimen:
Participants will receive subcutaneous injections once weekly (QW) during Cycle 1 (C1) for a total of 4 doses. Starting from Cycle 2 (C2), participants will transition to receiving subcutaneous injections once every two weeks (Q2W).
干预措施: HS-20117-2 Injection (Drug)
HS-20117-2 Injection Q3W Dosing Regimen:
Participants will receive subcutaneous injections once weekly (QW) during Cycle 1 (C1) for a total of 3 doses. Starting from Cycle 2 (C2), participants will transition to receiving subcutaneous injections once every three weeks (Q3W).
干预措施: HS-20117-2 Injection (Drug)
结局指标
主要结局
Evaluation of PK parameters of HS-20117: Cmax
时间窗: Up to Day 1 of Cycle 2（once every two weeks, each cycle is 14 days） or Day 1 of Cycle 3（once every three weeks, each cycle is 21 days）
Maximum concentration
Evaluation of PK parameters of HS-20117: Ctrough
时间窗: Up to Day 1 of Cycle 2（once every two weeks, each cycle is 14 days） or Day 1 of Cycle 3（once every three weeks, each cycle is 21 days）
Trough concentration
Evaluation of PK parameters of HS-20117: AUC0-14day
时间窗: Up to 14 days（once every two weeks）
Area under the plasma concentration-time curve fom time 0 to 14day
Evaluation of PK parameters of HS-20117: AUC0-21day
时间窗: Up to 21 days（once every three weeks）
Area under the plasma concentration-time curve fom time 0 to 21day
Evaluation of the safety and tolerability of HS-20117-2 Injection in patients with advanced solid tumors
时间窗: Through study completion,up to 2 years
Frequency of Adverse Events
次要结局
未报告次要终点