A Phase I, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HSK42360 in Pediatric Patients With BRAF V600-Mutant Malignant Brain Tumors

Haisco Pharmaceutical Group Co., Ltd.6 个研究点分布在 1 个国家目标入组 159 人开始时间: 2025年8月15日最近更新: 2025年9月8日

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方
入组人数: 159
试验地点: 6
主要终点: MTD

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a phase I, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, PK of HSK42360 when given orally in pediatric patients with active BRAF V600 mutation recurrent malignant brain tumors.

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 ≥6 and <18 years.
•Karnofsky/Lansky Performance Status >
•Life expectancy ≥ 3 months.
•Patients with recurrent malignant brain tumors confirmed by histology or cytology, who have failed standard treatment (disease progression after treatment or intolerable treatment); patients who have previously received BRAF and/or MEK inhibitor therapy are allowed to be included in this study.
•Positive BRAF V600 mutation result confirmed prior to the administration of HSK
•Patients will provide blood or tumor sample according to their own willingness.
•Measurable disease by RANO criteria.
•Patients with inactive CNS lesions, or patients treated with ≤5mg/day corticosteroid and without convulsion for ≥2 weeks.
•Adequate hematologic, hepatic, and renal function.
•Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose.

排除标准

•Patients with NF1 mutation.
•malignant tumor within 2 years, with the exception of cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, or other tumors with low malignancy.
•Uncontrollable pleural effusion, ascites, or pericardial effusion per protocol.
•Treatment with any of the following:
•Prior treatment with anti-tumor drug within 4 weeks or approximately 5 × t1/2 prior to the first dose of HSK42360, whichever is shorter; Prior treatment with nitrosourea or mitomycin C within 6 weeks prior to the first dose of HSK42360; Prior treatment with palliative radiotherapy or anti-tumor herbs within 2 weeks prior to the first dose of HSK42360; Prior treatment with radiotherapy, electric field therapy, or other anti-tumor therapies within 4 weeks prior to the first dose of HSK
•Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia, dermal toxicity, and other toxicity considering no safety risks by investigator.
•Any disease which would preclude drug absorption, metabolism or pharmacokinetics, eg. active peptic ulcer or chronic gastroesophageal reflux disease.
•Patient who have clinically significant or uncontrolled cardiac disease, include: QTc interval ≥ 450 msec; any clinically significant arrhythmia; left ventricular ejection fraction < 50%; myocardial infarction, unstable angina, or class III/IV cardiac failure by the NYHA that occurred within 6 months prior to the first dose of HSK
•Any thromboembolic events within 6 months prior to the first dose of HSK42360; any familial or aquired thrombophilia.
•Any unstable systemic disease, eg. severe metabolic disease: liver cirrhosis, renal failure, or uremia.
•Treatment with inhibitors/inducers for CYP3A4, or substrates of CYP3A4, CYP2C9, CYP2C8, OATP1B1, OATP1B3, OAT1, OAT3, P-gp or BCRP within 14 days or approximately 5 × t1/2 prior to the first dose of HSK42360, whichever is shorter.
•Patient with cognitive dysfunction, or history of mental illness, other uncontrolled comorbidities, alcohol dependence, hormone dependence or drug abuse.
•Autologous transplantation surgery within 3 months prior to the first dose of HSK42360; Allogeneic transplantation, or stem-cell Transplant surgery within 6 months prior to the first dose of HSK42360; Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of HSK
•Patient with a history of immunodeficiency, including HIV positive, or other acquired/congenital immunodeficiency diseases.
•Patient with severe retinal abnormalities and uveitis.
•Patient with active hepatitis B or hepatitis C.
•Allergic to any HSK42360 active constituent or ingredients.
•Participate in other clinical trials within 4 weeks prior to the first dose of HSK
•Positive pregnancy test, or breastfeeding.
•Any other circumstances that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

研究组 & 干预措施

Phase Ia: HSK42360 as monotherapy

Experimental

Phase 1a: dose escalation of HSK42360 as monotherapy at various dose levels

干预措施: HSK42360 (Drug)

Phase Ib: HSK42360 as monotherapy

Experimental

Phase 1b: dose expansion for HSK40118 as monotherapy at a dose determined during Phase 1a in patients with BRAF V600 recurrent mutation malignant brain tumors

干预措施: HSK42360 (Drug)