A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of SNH-118110 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Safety evaluation
研究概览
简要总结
This is a multicenter, open-label, Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of SNH-118110 administered orally. The study consists of a dose-escalation phase and a dose-expansion phase.
详细描述
This first-in-human, open-label, multicenter Phase I study is designed to assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of SNH-118110 administered orally. The study comprises two sequential parts: a dose-escalation phase to identify the maximum tolerated dose (MTD) or maximum administered dose (MAD), followed by a dose-expansion phase to further evaluate safety and anti-tumor activity. The primary endpoints include safety, MTD, and/or MAD.
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
- •Ability to understand and voluntarily sign an informed consent form (ICF) prior to any study related procedures.
- •Age ≥ 18 years at the time of signing the ICF.
- •Histologically or cytologically confirmed diagnosis of advanced solid tumors, with the following additional requirements:
- •Dose-escalation phase: Patients with advanced solid tumors harboring a RET gene alteration who have failed standard therapy or are intolerant to standard therapy.
- •Dose-expansion phase:
- •Cohort 1: Locally advanced or metastatic NSCLC with RET gene fusion who have progressed after at least one prior line of therapy, which must include a RET inhibitor.
- •Cohort 2: Treatment-naïve patients with locally advanced or metastatic NSCLC harboring a RET gene fusion.
- •Cohort 3: Other advanced solid tumors harboring RET gene alterations.
- •At least one measurable target lesion according to RECIST version 1.
- •Documentation of a RET fusion or other activating RET gene alteration (based on a local or central laboratory report).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no deterioration within the 2 weeks prior to the first dose of study drug.
- •Life expectancy of at least 3 months.
排除标准
- •Presence of other known oncogenic driver mutations.
- •Prior anti-tumor therapy within specified washout periods prior to first dose (e.g., small molecules, biologics, radiotherapy, major surgery), or failure to recover from clinically significant toxicities.
- •Clinically significant uncontrolled or active conditions, including but not limited to:
- •Inadequate bone marrow, hepatic, or renal function. Significant cardiovascular disease (e.g., uncontrolled hypertension, prolonged QTc, poor ejection fraction, recent thromboembolic events).
- •Active or uncontrolled infections, bleeding diathesis, or significant pleural/abdominal/pericardial effusion requiring intervention.
- •Central nervous system metastases unless stable and asymptomatic off steroids.
- •Conditions affecting oral drug absorption or gastrointestinal function.
- •History of severe allergic reactions to similar agents.
- •Pregnant or lactating women, or patients with serious concurrent medical or psychiatric conditions that would compromise safety or study compliance.
研究组 & 干预措施
SNH-118110
Dose escalation: Multiple doses of SNH-118110 Dose expansion: MTD/MAD/recommended expansion dose
干预措施: SNH-118110 Soft Capsules (Drug)
结局指标
主要结局
Safety evaluation
时间窗: Up to approximately 2 years
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Maximum tolerated dose (MTD) or maximum administered dose (MAD)
时间窗: Cycle 1 (up to 21 days)
Determination of the MTD or MAD of oral SNH-118110 by the number of participants who experience a dose limiting toxicity (DLT)
次要结局
- The maximum concentration (Cmax)(Cycle 1 day 1 through cycle 2 day 1 (cycle= 21 days))
- Time of the maximum concentration (Tmax)(Cycle 1 day 1 through cycle 2 day 1 (cycle= 21 days))
- Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t)(Cycle 1 day 1 through cycle 2 day 1 (cycle= 21 days))
- Elimination half-life (t1/2)(Cycle 1 day 1 through cycle 2 day 1 (cycle= 21 days))
- Objective response rate (ORR)(Up to approximately 2 years)
- Disease control rate (DCR)(Up to approximately 2 years)
- Duration of response (DoR)(Up to approximately 2 years)
- Progression-free survival (PFS)(Up to approximately 2 years)
- Overall survival (OS)(Up to approximately 2 years)