Phase I Study of HRS-6093 in Participants With Advanced Solid Tumors Harboring KRAS G12D Mutations

Официальное название

A Phase I Study of HRS-6093 Evaluating Safety, Tolerability, and Pharmacokinetics in Participants With Advanced Solid Tumors Harboring KRAS G12D Mutations

Обзор

This is an open-label, multi-center phase I clinical study to evaluate HRS-6093 Safety, Tolerability, and Pharmacokinetics in Participants harboring KRAS G12D Mutations with advanced solid tumors. The study consists of dose escalation, dose expansion and efficacy expansion.

Вмешательства

• Препарат HRS-6093
  HRS-6093

Первичные конечные точки

• Incidence and severity of adverse events/serious adverse events (graded as per CTCAE v5.0). [Срок оценки: Screening Period to 30 Days After the Last Dose]
• DLT, [Срок оценки: from day1 to day 23; 23 Days]
• MTD, [Срок оценки: from day1 to day 23; 23 Days]
• RP2D , [Срок оценки: 24 months]

Вторичные конечные точки (12)

• Number of Participants With Abnormal Laboratory Values [Срок оценки: Screening Period to 30 Days After the Last Dose; 24 months]
• Number of subjects with clinically significant changes in ECOG, vital signs and physical examination. [Срок оценки: Screening Period to 30 Days After the Last Dose; 24 months]
• Number of subjects with changes on ECG. [Срок оценки: Screening Period to 30 Days After the Last Dose; 24 months]
• maximum plasma concentration (Cmax), [Срок оценки: Screening Period to Day of the end of treatment/withdrawal. 24 months]
• time to maximum concentration (Tmax), [Срок оценки: Screening Period to Day of the end of treatment/withdrawal. 24 months]
• area under concentration-time curve from time 0 to the last measurable concentration time point t (AUC0-t), [Срок оценки: Screening Period to Day of the end of treatment/withdrawal. 24 months]
• Area under concentration-time curve from time 0 to infinity (AUC 0-∞), apparent volume of distribution (Vz/F), [Срок оценки: Screening Period to Day of the end of treatment/withdrawal. 24 months]
• elimination half-life (t1/2), and apparent clearance (CL/F); [Срок оценки: Screening Period to Day of the end of treatment/withdrawal. 24 months]
• minimum concentration at steady state (Cmin, ss), [Срок оценки: Screening Period to Day of the end of treatment/withdrawal. 24 months]
• area under the blood concentration-time curve at steady state (AUCss), and accumulation ratio (Rac); [Срок оценки: Screening Period to Day of the end of treatment/withdrawal. 24 months]
• objective response rate (ORR), [Срок оценки: Screening Period to PD; 24 months]
• duration of response (DoR), [Срок оценки: Screening Period to PD; 24 months]

Критерии участия

Критерии включения

• Have fully understood this study and are willing to sign the ICF, with good compliance and cooperation in follow-up;
• Aged between 18-75 years, with no gender requirement;
• Participants with histologically/cytologically confirmed advanced solid tumors who have been previously tested or are confirmed by the central laboratory to harbor KRAS G12D mutations; Have failed standard treatment, are intolerant to standard treatment, or have not received standard treatment.
• ECOG performance status (PS) score of 0 or 1;
• Life expectancy > 3 months;
• At least one measurable lesion per RECIST v1.1; A tumor tissue sample must be provided.
• Adequate organ function

Критерии исключения

• Toxicity (e.g., gastrointestinal reaction and skin toxicity) from prior anti-tumor treatment has not recovered to Grade ≤ 1 or a level specified in the inclusion/exclusion criteria;
• Presence of central nervous system (CNS) metastases;
• Participants with gastrointestinal diseases that affect drug administration/absorption
• Participants who have undergone major surgery other than diagnosis or biopsy within 28 days before the first dose, or are expected to undergo major surgery during the study period;
• Presence of serious pulmonary diseases
• Active tuberculosis or a history of active tuberculosis infection within 48 weeks prior to screening, regardless of whether they have been treated;
• Active or persistent gastrointestinal bleeding within 6 months prior to screening;
• History of allogeneic bone marrow or solid organ transplantation;
• History of deep vein thrombosis or pulmonary embolism within 6 months prior to screening;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring clinical intervention;
• Positive human immunodeficiency virus (HIV) (HIV1/2 antibodies), active chronic hepatitis B, or active hepatitis C (positive HCV antibody and positive HCV RNA);
• Known history of hypersensitivity to any component of the drug product to be used in the study;

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

• Shanghai Jiao Tong University School of Medicine — Шанхай
• West China Hospital of Sichuan University — Чэнду

Идентификаторы

NCT: NCT07134998 · HRS-6093-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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