A First-in-Human, Open-Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of JSKN027 in Patients With Advanced Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a first-in-human, open-label, multicenter Phase 1 (Ia/Ib) clinical study conducted in China to evaluate the safety and tolerability of JSKN027 in patients with advanced malignant solid tumors. The study will also assess the pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of JSKN027, and determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D).
The study includes two parts. Part Ia is a dose-escalation phase designed to evaluate the safety and tolerability of increasing dose levels of JSKN027. Part Ib is a dose-expansion phase in which additional patients will be enrolled at selected dose levels to further evaluate safety and preliminary antitumor activity in specific tumor types. Initial expansion cohorts are planned for patients with colorectal cancer, non-small cell lung cancer, and hepatocellular carcinoma.
详细描述
This is a first-in-human, open-label, multicenter Phase 1 (Ia/Ib) clinical study conducted in China to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of JSKN027 in patients with advanced malignant solid tumors, and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D).
The study consists of two parts: a dose-escalation phase (Part Ia) and a dose-expansion phase (Part Ib). In Part Ia, an accelerated titration design followed by an i3+3 dose-escalation design will be used to evaluate multiple dose levels of JSKN027 and assess its safety and tolerability. In Part Ib, multiple expansion cohorts will be enrolled based on tumor type to further evaluate the safety and preliminary efficacy of JSKN027 at selected dose levels. Initial expansion cohorts are planned for patients with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and hepatocellular carcinoma (HCC).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at the time of signing the ICF.
- •ECOG performance status 0-
- •Estimated life expectancy ≥ 3 months.
- •Histologically or cytologically confirmed advanced or metastatic malignant solid tumor.
- •For dose escalation (Part Ia): disease has progressed on standard therapy.
- •For dose expansion (Part Ib): participants with prespecified tumor types (e.g., colorectal cancer, non-small cell lung cancer, hepatocellular carcinoma, and other selected solid tumors) who have progressed on standard therapy.
- •At least one measurable extracranial lesion per RECIST v1.
- •Adequate bone marrow function within 7 days prior to enrollment (e.g., ANC ≥ 1.5×10^9/L, hemoglobin ≥ 90 g/L, platelets ≥ 100×10^9/L).
- •Adequate hepatic function within 7 days prior to enrollment (e.g., total bilirubin, AST/ALT, ALP within protocol-defined limits; albumin ≥ 30 g/L).
- •Adequate renal function within 7 days prior to enrollment (e.g., serum creatinine ≤ 1.5×ULN or creatinine clearance ≥ 60 mL/min; urine protein within acceptable limits).
- •Adequate coagulation function within 7 days prior to enrollment (e.g., PT/INR and aPTT within protocol-defined limits).
- •Adequate cardiac function (e.g., LVEF ≥ 50%).
- •Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
- •Participants of reproductive potential agree to use highly effective contraception from ICF signing until 7 months after the last dose.
排除标准
- •Active central nervous system (CNS) disease (e.g., active brain metastases or leptomeningeal disease).
- •Received an investigational agent within 28 days or 5 half-lives (whichever is shorter) prior to first dose.
- •Major surgery within 28 days prior to first dose or planned major surgery during the study.
- •History of severe immune-related adverse events or prior toxicity that would preclude safe participation, as judged by the investigator.
- •Significant gastrointestinal disorders that increase risk of perforation, bleeding, obstruction, or interfere with study participation.
- •Active or uncontrolled interstitial lung disease (ILD) or non-infectious pneumonitis, or suspected ILD/pneumonitis at screening.
- •Active autoimmune disease requiring systemic immunosuppression (exceptions may apply for limited, stable conditions).
- •Active hepatitis B or C, HIV infection, or other clinically significant immunodeficiency/infection not adequately controlled per local standards.
- •Prior allogeneic organ or bone marrow transplant.
- •Known hypersensitivity to the study drug or its excipients, or history of severe hypersensitivity to similar biologic agents.
- •Pregnant or breastfeeding.
- •Any condition that, in the investigator's judgment, would compromise participant safety or compliance.
研究组 & 干预措施
JSKN027
Participants will receive JSKN027 administered by intravenous infusion at dose levels based on actual body weight (mg/kg). The planned dose levels are 1, 3, 6, 10, 15, and 20 mg/kg, administered once every 3 weeks (Q3W).
干预措施: JSKN027 (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: From first dose of JSKN027 through 21 days after the first dose (DLT evaluation period)
The number of participants who experience dose-limiting toxicities (DLTs) during the dose-limiting toxicity evaluation period following administration of JSKN027
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From first dose of JSKN027 through 30 days after the last dose
The number of participants who experience treatment-emergent adverse events (TEAEs) following administration of JSKN027, graded according to NCI CTCAE version 5.0.
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of JSKN027
时间窗: From first dose of JSKN027 through completion of dose-escalation phase (approximately 12 months)
Determination of the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of JSKN027 based on observed dose-limiting toxicities and overall safety and tolerability.
次要结局
- Objective Response Rate (ORR) as Assessed by RECIST v1.1(From first dose of JSKN027 until disease progression or death, up to 24 months)
- Disease Control Rate (DCR) as Assessed by RECIST v1.1(From first dose of JSKN027 until disease progression or death, up to 24 months)
- Duration of Response (DoR) as Assessed by RECIST v1.1(From first documented response until disease progression or death, up to 24 months)
- Progression-Free Survival (PFS)(From first dose of JSKN027 until disease progression or death, up to 24 months)
- Overall Survival (OS)(From first dose of JSKN027 until death from any cause, up to 36 months)