Phase 1/2 Study of HS-10370 in Patients with Advanced Solid Tumors

Официальное название

A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10370 Monotherapy in Patients with Advanced Solid Tumors

Обзор

HS-10370 is an oral, highly selective, small molecular inhibitor of KRAS G12C. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10370 in Chinese advanced solid tumor patients.

Подробное описание

This is a phase 1/2, first-in-human, open-label, multicenter study of HS-10370, this study has two parts: phase 1 and phase 2. The phase 1 portion consists of dose escalation and dose expansion, which is aimed to assess the safety and tolerability of HS-10370 in subjects with advanced solid tumors and evaluate the preliminary efficacy of HS-10370. Phase 2 will be conducted to evaluate the efficacy of HS-10370 in subjects with locally advanced or metastatic NSCLC with a KRAS G12C mutation.

Вмешательства

• Препарат HS-10370
  HS-10370 will be administered orally once daily in a continuous regimen

Первичные конечные точки

• Phase Ia：To determine the maximum tolerated dose (MTD) [Срок оценки: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days).]
• 2. Phase Ib/II: To evaluate clinical activity/efficacy of HS-10370 by assessment of objective response rate [Срок оценки: up to 24 months]

Вторичные конечные точки (8)

• Incidence and severity of treatment-emergent adverse events [Срок оценки: From baseline until 28 days after the last dose]
• Observed maximum plasma concentration (Cmax) after single dose of HS-10370 [Срок оценки: From pre-dose to 120 hours after single dose on Day 1]
• Time to reach maximum plasma concentration (Tmax) after single dose of HS-10370 [Срок оценки: From pre-dose to 120 hours after single dose on Day 1]
• Apparent terminal half-life (T1/2) after single dose of HS-10370 [Срок оценки: From pre-dose to 120 hours after single dose on Day 1]
• Duration of response (DOR) [Срок оценки: 24 months]
• Disease Control Rate (DCR) [Срок оценки: 24 months]
• Progression-free survival (PFS) [Срок оценки: 24 months]
• Overall survival (OS) [Срок оценки: 24 months]

Критерии участия

Критерии включения

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:

• Men or women greater than or equal to 18 years
• Locally advanced or metastatic cancer patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable
• Pathological, tumor tissue samples can be used to test KRAS G12C mutation by central laboratory for Phase 1b subjects.
• At least one measurable lesion in accordance with RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status: 0\~1
• Estimated life expectancy >12 weeks
• Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.
• Females must have the evidence of non-childbearing potential
• Signed and dated Informed Consent Form

Критерии исключения

• Treatment with any of the following:

• Previous or current treatment with KRAS G12C inhibitors
• Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10370
• Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10370
• Local radiotherapy for palliation within 2 weeks of the first dose of HS-10370, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10370
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10370
• Inadequate bone marrow reserve or serious organ dysfunction
• Uncontrolled pleural, ascites or pericardial effusion
• Known and untreated, or active central nervous system metastases
• Active autoimmune diseases or active infectious disease
• Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications
• History of hypersensitivity to any active or inactive ingredient of HS-10370 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10370
• The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator
• The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator
• Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study
• History of neuropathy or mental disorders, including epilepsy and dementia

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology — Ухань

Идентификаторы

NCT: NCT05367778 · HS-10370-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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