Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors

Официальное название

A Phase 1/2, Open-Label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Preliminary Efficacy of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors

Обзор

The study has consists of two parts, a dose escalation part (Part 1) and a dose selection optimization part (Part 2). The primary objectives of this study are to evaluate the safety and tolerability of ISM3412 in participants with locally advanced/metastatic solid tumors, and to determine the RP2D of ISM3412.

Вмешательства

• Препарат ISM3412
  ISM3412 will be administered orally once daily.

Первичные конечные точки

• Incidence of dose-limiting toxicity (DLT) events [Срок оценки: 31 days]
• Incidence and severity of adverse events (AEs) [Срок оценки: Approximately 30 months]
• Recommended phase 2 dose (RP2D) [Срок оценки: Approximately 30 months]

Вторичные конечные точки (7)

• Maximum observed concentration (Cmax) [Срок оценки: Approximately 30 months]
• Time of maximum observed concentration (Tmax) [Срок оценки: Approximately 30 months]
• Area under the concentration-time curve (AUC) [Срок оценки: Approximately 30 months]
• Terminal half-life (t1/2) [Срок оценки: Approximately 30 months]
• Objective response rate (ORR) [Срок оценки: Approximately 30 months]
• Best objective response (BOR) [Срок оценки: Approximately 30 months]
• Duration of response (DoR) [Срок оценки: Approximately 30 months]

Критерии участия

Критерии включения

• Male or female participants with age ≥18 years at the time of signing the informed consent.
• Histologically confirmed unresectable locally advanced or metastatic solid tumors with confirmed homozygous MTAP deletion, who have disease progression after standard therapy, intolerable to standard therapy, or for whom no standard therapy exists.
• Have measurable or evaluable lesions in Part 1 and at least one measurable target lesion in Part 2 as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• ECOG PS (Eastern Cooperative Oncology Group Performance Status) ≤1.
• Life expectancy of ≥12 weeks as judged by the investigator.
• Adequate organ function as determined by medical assessment.
• Capable of providing signed ICF and complying with the requirements and restrictions listed in the ICF and in this study protocol.

Критерии исключения

• Prior treated with other MAT2A inhibitors and/or PRMT inhibitors.
• Participation in other therapeutic clinical studies within 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment.
• Anti-tumor therapy (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or other anti-tumor therapy, except for hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogues, agonists required to suppress serum testosterone levels) within 28 days or 5 half-lives, whichever is shorter prior to first dose of study treatment.
• Toxicities of prior therapy have not resolved to Grade ≤1 or to baseline (as evaluated by NCI CTCAE version 5.0)
• History of another primary tumor that has been diagnosed or required therapy within the past 3 years.
• Previous history of, or presence of Gilbert's syndrome.
• Previous history of myelodysplastic syndrome.
• Prior solid organ or hematopoietic stem cell transplant.
• Known active central nervous system (CNS) primary tumor or untreated CNS metastases.
• Have serious cardiovascular or cerebrovascular disease as per protocol.
• Presence of uncontrolled systemic infection as per protocol.
• Unwillingness or unable to comply with the requirements of oral drug administration, or presence of a gastro-intestinal condition.

Other protocol inclusion and exclusion criteria may apply.

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

США · 5 центров

• Sarah Cannon Research Institute at HealthONE — Denver
• Smilow Cancer Hospital at Yale New Haven Breast Center — New Haven
• Community Cancer Center North — Indianapolis
• SCRI Oncology Partners — Nashville
• The University of Texas MD Anderson Cancer Center — Houston

Китай · 5 центров

• Cancer Hospital Chinese Academy of Medical Sciences — Пекин
• Peking University People's Hospital — Пекин
• Sun Yat-sen university cancer center — Гуанчжоу
• Jiangsu Provincial People's Hospital — Нанкин
• Shanghai Gobroad Cancer Hospital — Шанхай

Идентификаторы

NCT: NCT06414460 · ISM3412-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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