A Clinical Study of HRS-8364 in the Treatment of Advanced Solid Tumor Subjects

Официальное название

An Open Label, Multicenter Phase I/II Clinical Study on the Safety, Tolerability, Pharmacokinetics, and Efficacy of HRS-8364 in the Treatment of Advanced Solid Tumor Subjects

Обзор

This study is an open, multicenter, Phase I/II clinical trial, divided into three stages: dose escalation, dose expansion and efficacy expansion.

Вмешательства

• Препарат HRS-8364 Tablet
  HRS-8364 tablet.

Первичные конечные точки

• The Dose-Limiting Toxicity (DLT) [Срок оценки: Post-dose at Day 1 to Day 21.]
• The Maximum Tolerated Dose (MTD) [Срок оценки: Post-dose at Day 1 to the end of treatment visit, about 1 year.]
• Recommended dosage for Phase II (RP2D) [Срок оценки: Post-dose at Day 1 to the end of treatment visit, about 1 year.]
• Incidence and severity of adverse events (AEs) [Срок оценки: From signing the informed consent form to safety follow-up completed, about 1 year.]
• Objective Response Rate (ORR) [Срок оценки: From the first administration to the end of treatment visit, about 1 year.]

Вторичные конечные точки (7)

• Maximum Concentration of HRS-8364 (Cmax) [Срок оценки: Day 1 pre-dose to the end of treatment visit, about 1 year.]
• Time to maximum plasma concentration (Tmax) [Срок оценки: Day 1 pre-dose to the end of treatment visit, about 1 year.]
• Area under the concentration versus time curve of HRS-8364 from time zero to time t (AUC0-t). [Срок оценки: Day 1 pre-dose to the end of treatment visit, about 1 year.]
• Bioaccumulation of HRS-8364 in postprandial relative fasting state. [Срок оценки: Cycle 0 Day1 pre-dose to Cycle 1 Day 3, about 6 days.]
• Duration of relief (DOR). [Срок оценки: From the first administration to the end of treatment visit, about 1 year.]
• Disease Control Rate (DCR). [Срок оценки: From the first administration to the end of treatment visit, about 1 year.]
• Progression-free survival (PFS). [Срок оценки: From the first administration to the end of treatment visit, about 1 year.]

Критерии участия

Критерии включения

• Voluntarily joining this study, signing an informed consent form, good compliance, and able to cooperate with follow-up.
• Age range: 18-75 years old (including boundary values), both males and females are eligible.
• Monotherapy dose escalation stage: advanced solid tumors diagnosed by cytology or histology, which have failed standard treatment or are intolerant to previous standard treatment or have no standard treatment.
• Monotherapy dose expansion stage: advanced solid tumors diagnosed by cytology or histology; with other systemic treatments during the recurrence or metastasis stage, and disease progression during or after treatment; The combined dose expansion phase allows for the inclusion of individuals who have not received prior treatment with immuno checkpoint inhibitors (ICIs).
• Efficacy expansion of monotherapy: advanced solid tumors diagnosed by histopathology or cytology; with other systemic treatments during the recurrence or metastasis stage, and disease progression during or after treatment.
• At least one measurable lesion that meets the RECIST v1.1 criteria.
• ECOG PS score: 0 to 1.
• Expected survival ≥ 12 weeks.
• Female subjects with reproductive ability and male subjects with partners who are reproductive women must agree to use efficient contraception during the trial period and within 30 days after the last dose of HRS-8364 (whichever comes later), have no fertility plan, and avoid donating eggs/sperm; Female subjects with fertility must have a negative blood pregnancy test within 7 days prior to the first administration and must be non-lactating.

Критерии исключения

• Untreated brain metastases; Or accompanied by meningeal metastasis, spinal cord compression, etc.
• Large blood vessels invasion confirmed by imaging, or the subject's tumor has a high possibility of invading important blood vessels and causing fatal bleeding during treatment judged by researchers.
• Uncontrolled pleural effusion, pericardial effusion, or peritoneal effusion accompanied by clinical symptoms.
• Severe bone damage caused by tumor bone metastasis, including uncontrolled severe bone pain, pathological fractures in important areas that have occurred or are expected to occur in the past 6 months, and spinal cord compression. Subjects who require analgesic medication must have a stable analgesic treatment plan in place at the time of entry into the study.
• Other malignant tumors in the past 5 years or at the same time.
• Major arterial/venous thrombotic events within 6 months prior to the first use of medication, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction (excluding asymptomatic lacunar cerebral infarction)), deep vein thrombosis (excluding asymptomatic and non anticoagulant intramuscular vein thrombosis), and pulmonary embolism.
• Past or current active interstitial lung disease requiring treatment, non-infectious pneumonia requiring glucocorticoid systemic therapy (such as radiation pneumonitis); Currently, individuals with active pneumonia or confirmed severe pulmonary ventilation dysfunction through lung function tests.
• Individuals with active pulmonary tuberculosis. Individuals who have undergone sufficient treatment and have stopped anti tuberculosis treatment for at least 3 months prior to their first medication can be enrolled in the study.
• Known to have a positive history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). Known to have active viral hepatitis.
• Unable to swallow pills normally or experiencing gastrointestinal dysfunction, which may affect drug absorption according to researchers' assessment.
• Individuals who have experienced intestinal obstruction or gastrointestinal perforation within 3 months prior to their first medication use.
• According to the researchers' assessment, there are other factors that may affect the research results or lead to the forced termination of this study, such as alcohol abuse, drug use, drug abuse, other serious illnesses (including mental illnesses) that require concurrent treatment, serious laboratory test abnormalities, and family or social factors that may affect medication safety.

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 · 2 центра

• The Sixth Affiliated Hospital, Sun-Yat-Sen University — Гуанчжоу
• Liaoning Cancer Hospital & Institute — Шэньян

Идентификаторы

NCT: NCT07446153 · HRS-8364-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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