A Phase I First-in-Human Study of GenSci128 in Patients With Solid Tumors Harboring a TP53 Y220C Mutation

Официальное название

A Phase I, Multicenter, Multinational, Open-label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of GenSci128 Tablet in Patients With Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation

Обзор

The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of GenSci128 Tablet in Patients with Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation

Вмешательства

• Препарат GenSci128 tablets
  GenSci128 tablets have three specifications, including 50mg, 200mg, 500mg, and are taken in combination with the doctor's advice in different dose levels. GenSci128 will be orally administrated daily (except single dose in Cycle 0) with no interruptions until occurrence of unacceptable toxicity, or progressive disease, or withdrawal of consent, or death, or contact lost, or starting a new anticancer therapy, etc. (whichever occurs first).

Первичные конечные точки

• Incidence and severity of adverse events (AEs) and dose limiting toxicities (DLTs) [Срок оценки: 3 weeks]
• maximal tolerance dose （MTD）、recommended dose of expansion （RDE） [Срок оценки: up to 3 months]
• recommended phase 2 dose （RP2D） [Срок оценки: up to 3 months]

Критерии участия

Критерии включения

• Has the ability to understand and the willingness to sign a written informed consent document (prior to the initiation dose of GenSci128 and any study procedures)
• Is willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures
• Has confirmed TP53 Y220C mutation in tumor tissue
• Has histologically or cytologically confirmed locally advanced or metastatic solid tumors and have progressed following standard therapy, or for whom, in the opinion of the investigator, no available and effective standard therapy exists.
• Has at least one measurable lesion by RECIST v1.1
• Has an ECOG status of 0 or 1
• Has a life expectancy of ≥ 3 months.

Критерии исключения

• Has diagnosed as primary central nervous system (CNS) tumor.
• Has CNS metastases, unless asymptomatic, neurologically stable and not requiring steroids treatment for at least 2 weeks prior to initiation dose of GenSci128.
• Has a history of leptomeningeal disease or spinal cord compression.
• Has stroke or transient ischemic attack within 6 months prior to initiation dose of GenSci128.
• Has active infection requiring intravenous (IV) antibiotics or other uncontrolled inter-current illness requiring hospitalization. Minor infections, e.g., periodontal infection or urinary tract infection (UTI), which may be treated with short term oral antibiotics are allowed.
• Uncontrolled hypertension (Blood pressure ≥ 150/90 mmHg despite optimal medical management)
• Has a history of prior organ transplant or allogeneic stem cell transplant.
• Has received a selective reactivator of p53 Y220C mutation.
• Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence ≤ 14 days after intervention).
• Has known human immunodeficiency virus (HIV) infection (positive HIV 1/2 antibodies) or known chronic hepatitis B or C \[participants positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA; participants positive for hepatitis C virus (HCV) IgG will be eligible if they are negative for HCV-RNA\].
• Is persisting toxicity related to prior anticancer therapy (NCI CTCAE V5.0 Grade>1). However, alopecia and sensory neuropathy Grade ≤2, or other Grade ≤2 adverse events not constituting a safety risk, based on the investigator's judgment are acceptable.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or GenSci128 administration or may interfere with the interpretation of study results, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhongshan Hospital ,Fudan University — Шанхай

Идентификаторы

NCT: NCT06908434 · GenSci128-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗