A Phase I/II of HRS-6719 in Patients With Advanced/Metastatic Solid Tumors

Официальное название

A Phase I/II, Open-label, Multi-centre Study Evaluating the Safety,Tolerability,Pharmacokinetic (PK), Pharmacodynamics, and Preliminary Efficacy of HRS-6719 in Patients With Advanced/Metastatic Solid Tumors With MTAP Deficiency

Обзор

This is a Phase I/II, multicenter, open-label clinical trial with dose escalation/dose expansion/efficacy expansion phases, designed to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic (PK/PD) profiles, and antitumor efficacy characteristics of HRS-6719 in patients with MTAP-deficient advanced solid tumors.

Вмешательства

• Препарат HRS-6719
  HRS-6719

Первичные конечные точки

• Dose Limited Toxicity (DLT) [Срок оценки: 21 Days (first cycle)]
• Maximum tolerable dose (MTD) [Срок оценки: 21 Days (first cycle)]
• Recommended dose for phase II (RP2D) [Срок оценки: through phase I completion, an average of 1 years]
• Incidence and severity of AE [Срок оценки: from Day1 to 30 days after last dose]

Вторичные конечные точки (7)

• Relative bioavailability after meals on an empty stomach [Срок оценки: through phase I completion, an average of 1 years]
• ORR [Срок оценки: 12 months after the last subject was enrolled in the group]
• DOR [Срок оценки: 12 months after the last subject was enrolled in the group]
• DCR [Срок оценки: 12 months after the last subject was enrolled in the group]
• TTR [Срок оценки: 12 months after the last subject was enrolled in the group]
• PFS [Срок оценки: 12 months after the last subject was enrolled in the group]
• OS [Срок оценки: 1 Year after last dose]

Критерии участия

Критерии включения

• Subjects must voluntarily participate in the study and sign an informed consent form;
• Aged 18-75 years, male or female eligible；
• ECOG performance status score of 0-1；
• Expected survival ≥12 weeks；
• Patients with histologically or cytologically confirmed advanced malignant solid tumors who meet one of the following criteria:Disease progression or intolerance after receiving adequate standard therapy; Lack of standard treatment options;Currently ineligible for standard therapy；
• Ability to provide sufficient fresh or archived tumor tissue specimens；
• Adequate function of vital organs；
• Effective contraception must be used during the trial. For women of childbearing potential, a negative pregnancy test within 7 days prior to the first dose is required。

Критерии исключения

• History of other malignant tumors within the past 5 years；
• Received systemic anti-tumor therapy within 4 weeks prior to the first study dose.
• Surgical procedures requiring tracheal intubation and general anesthesia were performed within 4 weeks before the first administration, diagnostic or surface surgery was performed within 1 week before the first administration, or elective surgery was expected during the trial.
• The study received radical radiotherapy within 4 weeks before the first medication ; and received palliative radiotherapy within 2 weeks before the first medication.
• Uncontrolled pleural, pericardial, or peritoneal effusions.
• Severe cardiac diseases occurring within 6 months prior to the first dose.
• Arterial/venous thrombosis within 6 months before the first dose.
• Clinically significant bleeding symptoms or predisposition within 3 months prior to the first dose.
• Active infection or fever of unknown origin > 38.5 ° C was present within 4 weeks before the first administration of the study
• History of immunodeficiency.
• Active hepatitis B or C.
• Diseases affecting drug absorption/transport (e.g., malabsorption syndromes).
• A history of severe allergic reactions to HRS-6719 and its main components was known or suspected, or there was a history of delayed allergic reactions, eczema or asthma that could not be controlled by topical corticosteroids.
• Use of strong CYP3A4/P-gp inhibitors/inducers within 5 half-lives before the first dose.
• Adverse events (AEs) from prior anti-tumor therapy not resolved to CTCAE v5.0 ≤ Grade 1.
• Patients with interstitial pneumonia or interstitial lung disease, or previous history of interstitial pneumonia or interstitial lung disease requiring hormone therapy, or clinically significant pulmonary fibrosis, persistent pneumonia, pneumonia caused by drug or radiotherapy, congenital pneumonia, or chest CT scan found any evidence of active pneumonia.
• Through medical history or CT examination, it was found that there was active pulmonary tuberculosis infection within 1 year before enrollment, or more than 1 year ago, there was a history of active pulmonary tuberculosis infection but no formal treatment.
• Live attenuated vaccines administered within 4 weeks before the first dose or planned during the study.
• Other factors potentially compromising study safety or data integrity.

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

• Barbin Medical University Cancer Hospital — Харбин
• Zhejiang Cancer Hospital — Ханчжоу

Идентификаторы

NCT: NCT06922357 · HRS-6719-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗