A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of HSK46256 in Patients With Advanced Solid Tumors

Официальное название

A Phase 1, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of HSK46256 Tablets in Patients With Advanced Solid Tumors

Обзор

This is a Phase 1, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HSK46256 tablets, a selective PARP1 inhibitor, in patients with advanced solid tumors. The study consists of a dose escalation phase and a dose expansion phase. In the dose escalation phase, a 3+3 dose escalation design will be used to evaluate multiple dose levels. The dose expansion phase will enroll patients into expansion cohorts at selected dose levels to further evaluate safety and preliminary efficacy.

Вмешательства

• Препарат HSK46256
  Oral administration. Dose escalation: an initial single-dose period followed by multiple-dose cycles until disease progression or intolerable toxicity. Dose expansion: multiple-dose cycles directly. Specific dose levels and dosing frequency will be determined based on dose-escalation data.

Первичные конечные точки

• DLTs [Срок оценки: Up to 24 days]
• MTD [Срок оценки: Up to 24 days]

Вторичные конечные точки (8)

• Progression-Free Survival (PFS) [Срок оценки: Up to 24 months]
• Duration of Response (DOR) [Срок оценки: Up to 24 months]
• Disease Control Rate (DCR) [Срок оценки: Up to 24 months]
• Radiographic Progression-Free Survival (rPFS, prostate cancer only) [Срок оценки: Up to 24 months]
• Objective Response Rate (ORR) [Срок оценки: Up to 24 months]
• PK parameters of HSK46256 [Срок оценки: Circle 1 (21 days)]
• Pharmacokinetic parameters of HSK46256 [Срок оценки: Circle 1 (21 days)]
• Pharmacokinetic parameters of HSK46256 [Срок оценки: Circle 1 (21 days)]

Критерии участия

Критерии включения

• Age ≥18 years, voluntarily participate and provide signed informed consent,
• ECOG performance status 0-1 or KPS >60; estimated life expectancy ≥12 weeks,
• Histologically or cytologically confirmed locally advanced or metastatic solid tumors, failed prior standard therapy, intolerant to standard therapy, or no available standard therapy,
• Dose escalation: prior treatment with one line of non-selective PARP inhibitor allowed,
• Documented HRR gene mutation,
• Agree to provide tumor tissue and/or blood samples,
• Fertile participants must agree to use effective contraception during study and for 3 months after last dose; negative pregnancy test for females,

Критерии исключения

• Other malignancies within past 2 years (except adequately treated basal cell carcinoma, squamous cell carcinoma, cervical carcinoma in situ, thyroid papillary carcinoma);
• Uncontrolled moderate to large pleural, pericardial, or peritoneal effusions;
• Prior anticancer therapy or concomitant use of CYP3A4 strong/moderate inhibitors/inducers within protocol-specified washout periods;
• Prior anticancer treatment toxicity not resolved to CTCAE ≤Grade 1 (except alopecia, skin toxicity);
• Any condition affecting drug swallowing or significantly impacting drug absorption/PK;
• Severe or uncontrolled cardiac disease (QTcF prolongation, significant arrhythmia, LVEF <50%, recent MI/heart failure);
• Arterial/venous thromboembolic events within 6 months deemed uncontrolled risk;
• Severe/uncontrolled diabetes, hypertension, active bleeding, epilepsy, COPD, interstitial lung disease, active systemic infection;
• Unstable systemic disease (severe hepatic/renal/metabolic disorders);
• Prior MDS or AML diagnosis, or history of hematopoietic stem cell transplantation;
• Major surgery or severe trauma within 4 weeks;
• HIV positive, active hepatitis B/C, or active syphilis;
• Known hypersensitivity to study drug or excipients;
• Participation in another interventional trial within 4 weeks;
• Pregnant or lactating women;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07695142 · HSK46256-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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