A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of HLX53 (an Anti-TIGIT Fc Fusion Protein) in Patients With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence of DLT
研究概览
简要总结
This phase I, first-in-human, open-label clinical study will evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of HLX53 (an anti-TIGIT Fc fusion protein) in patients with advanced/metastatic solid tumors.
详细描述
This study is an open-label phase I clinical study to evaluate the safety, tolerability , PK/PD and preliminary efficacy of HLX53 in patients with advanced/metastatic solid tumor. 11-30 subjects with advanced or metastatic solid tumors will be enrolled. The accelerated titration and traditional 3 + 3 dose escalation design will be implemented. Subjects will receive intravenous infusion of HLX53 at different doses according to the order of enrollment. There are 5 preset dose groups, namely 30mg/QW, 150mg/QW, 400mg/QW, 1000mg/Q3W and 2000mg/Q3W, administered by intravenous infusion. Observation period of DLT will last for 21 days after the first administration of HLX53. Maximum tolerated dose (MTD) definition: The highest dose level at which no more than 1 of 6 DLT-evaluable subjects developed DLT. At the MTD dose, at least 6 subjects were evaluable for DLT. When the MTD is determined, the MTD is usually used as the RP2D, or the RP2D is determined based on safety, PK/PD/ADA/NAb characteristics, and potential clinical efficacy.
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
- •Voluntary participation in clinical studies, full understanding of the trial, and signing of informed consent, willingness to follow and ability to complete the study in accordance with the requirements of the trial protocol.
- •histologically or cytologically confirmed advanced/metastatic solid tumors or lymphoma, failure of standard therapy, or no standard therapy.
- •Age ≥ 18 years and ≤ 75 years at the time of informed consent.
- •Eastern Cooperative Oncology Group (ECOG) score 0 or
- •At least one measurable lesion according to RECISTv1.1 or 2014 Lugano (lymphoma) response evaluation criteria.
- •Life expectancy of more than three months.
- •Adequate hematological function.
- •Adequate liver function.
- •Adequate renal function
- •Adequate cardiac function.
- •Male and female subjects of childbearing potential must agree to use at least 1 highly effective method of contraception during the trial and for at least 6 months after the last dose of study drug.
排除标准
- •Known history of serious allergy to the components of HLX53 or to any monoclonal antibody.
- •Prior treatment with anti-TIGIT or antibody to the relevant target CD155, CD112, or CD
- •Unresolved toxicity after prior antineoplastic therapy, i.e., not resolved to baseline, Grade 0-1 per NCI-CTCAE 5.0 (except alopecia).
- •Coexisting unstable or controlled medical conditions.
- •Spinal cord compression with clinical symptoms.
- •Prior allogeneic bone marrow transplant or solid organ transplant.
- •History of primary immunodeficiency.
- •History of eczema or asthma that cannot be controlled by topical corticosteroids.
- •History of any second malignancy within 2 years, except for curatively treated early malignancies (carcinoma in situ or stage I tumors) such as non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, ductal carcinoma in situ of the breast, papillary thyroid cancer.
- •Vaccination with a live attenuated vaccine within 4 weeks prior to the first dos.e
- •Use of immunosuppressive drugs within 2 weeks prior to initial administration.
- •Received major surgery, anti-tumor therapy (chemotherapy, radiotherapy, targeted therapy, immunotherapy or biological therapy) within 4 weeks prior to the first dose.
- •Known to have active infectious disease such as active HBV, HCV infection.
- •History of human immunodeficiency virus (HIV) infection.
- •Pregnancy or lactation.
结局指标
主要结局
Incidence of DLT
时间窗: Up to 3 weeks.
Ratio of the number of patients with DLT events in each dose group to the number of patients in the dose group during the DLT evaluation period.
MTD
时间窗: Up to 3 weeks
The maximum tolerated dose (MTD) of HLX53
RP2D
时间窗: Through study completion, assessed up to 2 years.
The recommended phase II dose (RP2D) of HLX53
Adverse event
时间窗: Through study completion, assessed up to 2 years.
Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 for patients receiving study drug.
次要结局
- t1/2(From baseline to 30 days after the last administration, assessed up to 7 months)
- Tmax(From baseline to 30 days after the last administration, assessed up to 7 months)
- Cmax(From baseline to 30 days after the last administration, assessed up to 7 months)
- Progression-free survival (PFS)(From date of the first HLX53 administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.)
- TIGIT Receptor Occupancy(From baseline to 30 days after the last administration，assessed up to 7 months)
- ADA(From baseline to 30 days after the last administration，assessed up to 7 months)
- Overall survival(OS)(From date of the first HLX53 administration until the date of death from any cause, whichever came first, assessed up to 2 years.)
- Objective response rate (ORR)(Through study completion, assessed up to 2 years.)