Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of HG381 as Monotherapy in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- HitGen Inc.
- 入组人数
- 57
- 试验地点
- 2
- 主要终点
- Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
This is a Phase I, first in human, open-label, non-randomized, multicenter study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy and establish a recommended dose of HG381 administered intravenously (IV) alone in subjects with advanced solid tumors.
详细描述
The trial consists of a dose escalation phase and a cohort expansion phase.In dose escalation phase, escalating doses of HG381 will be evaluated as guided by the traditional 3+3 design . In cohort expansion phase, subjects will receive HG381 alone at a single dose level determined based on the data form dose escalation phase. In total, approximately 57 subjects will participate in the study, approximately 42 in the dose-escalation cohort, and approximately 15 in the expansion cohort.
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
- •Capable of giving signed informed consent.
- •Life expectancy of at least 3 months.
- •Histological or cytological documentation of an advanced solid tumor，subjects with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.
- •Measurable disease per RECIST version 1.1, there is at least one measurable lesion during the screening period.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
- •Adequate organ function : Hematologic system: Hemoglobin ≥9 g/dL, Absolute neutrophil count [ANC] ≥1.5x10^9/L, Platelets ≥100x10^9/L, INR ≤ 1.5 and APTT ≤1.5 x ULN; Hepatic system: Total bilirubin ≤1.5 x ULN, ALT and AST ≤ 2.5 x ULN; Renal system: serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min (calculated by the Cockcroft-Gault formula); Cardiac system: left ventricular ejection fraction (LVEF) ≥50% ; QT interval (QTcF) ≤470 ms for women, and ≤450 ms for men; Endocrine system: Thyroid-stimulating hormone (TSH) is within the normal limits.
- •Subjects with fertility must agree to take medically approved effective contraceptive measures during the entire trial period and at least 3 months after the last medication.
排除标准
- •Chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anticancer therapy within 4 weeks.
- •Concurrent medical condition requiring the use of other systemic immunosuppressive treatment within 4 weeks before the first dose of study treatment.
- •Receipt of any live vaccine within 4 weeks of the start of study treatment.
- •Receipt of unmarketed clinical trial drugs or treatments within 4 weeks of the start of study treatment.
- •Receipt of surgery or interventional treatment (excluding tumor biopsy, puncture, etc.) within 4 weeks of the start of study treatment.
- •History or evidence of cardiovascular and cerebrovascular diseases risk.
- •Subjects with uncontrolled diabetes.
- •Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.
- •Currently or in the past suffering from malignant tumors.
- •Uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently after appropriate intervention.
- •Active or suspected autoimmune disease.
- •History of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis.
- •Toxicity from previous treatment including: Toxicity Grade ≥3 related to prior immunotherapy and that led to study treatment discontinuation; Toxicity related to prior treatment that has not resolved to Grade ≤
- •Subjects who have acute bacterial, viral or fungal infections and require systemic anti-infective treatment.
- •Positive test for syphilis antibodies or human immunodeficiency virus (HIV) antibodies.
- •Subjects who are allergic to test drugs and excipients.
- •Women who are pregnant or breastfeeding.
- •Known drug or alcohol abuse.
- •Patients with mental or neurological diseases.
- •Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
- •Subjects who have a history of serious systemic disease or any other reason are not suitable to participate in this trial as judged by the investigator.
研究组 & 干预措施
Part B: HG381 Monotherapy Dose Expansion Cohort
Subjects will be administered the recommended Phase 2 dose of HG381 IV Q1W established in Part A of the study.
干预措施: HG381 (Drug)
Part A: HG381 Monotherapy Dose Escalation Cohort
Subjects will receive HG381 IV at every one week intervals (Q1W). Escalating doses of HG381 will be evaluated by the traditional 3+3 design.
干预措施: HG381 (Drug)
结局指标
主要结局
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
时间窗: Up to 24 months
An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or requires medical judgement.
Maximum Tolerated Dose (MTD)
时间窗: Up to 12 months
The maximum tolerated dose (MTD) is defined as the maximum dose where the number of cases of DLT ≤ 1/6 of the total number of cases during the DLT observation period. At least 6 evaluable subjects are required to determine MTD.
Severity of AEs
时间窗: Up to 24 months
The severity of AEs will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Number of subjects achieving Dose-limiting toxicity (DLT)
时间窗: Up to Day 21
DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.
次要结局
- Best objective response based on RECIST 1.1(Up to 24 months)
- Recommended Phase 2 Dose (RP2D) of HG381(Up to 12 months)
- Maximum observed concentration (Cmax) following administration of HG381 alone(Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days))
- HG381 concentrations in plasma following administration of HG381 alone(Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days))
- Apparent terminal phase half-life (t½) following administration of HG381 alone(Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days))
- Area under the concentration-time curve (AUC) following administration of HG381 alone(Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days))