A Phase I/II Study of AST-001 in Subjects With Advanced Solid Tumors

Официальное название

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Efficacy and Correlation With AKR1C3 Enzyme Expression of AST-001 in Subjects With Advanced Solid Tumors

Обзор

A first-in-human open-label, Phase I/II study to evaluate the safety, tolerability, MTD/RP2D, PK, and preliminary efficacy of AST-001 administered as a single agent.

Вмешательства

• Препарат AST-001
  liquid formulation for Intravenous infusion

Первичные конечные точки

• Incidence and severity of adverse events (AEs) [Срок оценки: Adverse events will be noted as it occurs. Timeframe for measure begins after informed consent until 30 days after last dose of study drug.]
• Assess safety changes in electrocardiogram (ECG) [Срок оценки: Day 1 of each cycle(there are 26 cycles; 28 days for each cycle)]
• Assess safety changes of body weight. [Срок оценки: pre-AST-001 infusion of each cycle (there are 26 cycles; 28 days for each cycle)]
• Number of participants with dose limiting toxicities (DLTs) [Срок оценки: Throughout Cycle 1 (28 days for each cycle)]
• Define the Recommended Phase 2 Dose (RP2D) [Срок оценки: Days 1, 8 and 15 of each cycle (all 26 cycles and there are 28 days for each cycle)]
• Pharmacokinetics (PK) - Time to maximum concentration (Tmax) [Срок оценки: Days 1 and 15 of Cycle 1 (first cycle of 26 cycles and there are 28 days for each cycle)]
• PK - Maximum peak plasma concentration (Cmax) [Срок оценки: Days 1 and 15 of Cycle 1 (first cycle of 26 cycles and there are 28 days for each cycle)]
• PK - Area under the concentration-time curve (AUClast) PK - Area under the concentration-time curve (AUClast) [Срок оценки: Days 1 and 15 of Cycle 1 (first cycle of 26 cycles and there are 28 days for each cycle)]
• PK - Half-life (T1/2) [Срок оценки: Days 1 and 15 of Cycle 1 (first cycle of 26 cycles and there are 28 days for each cycle)]
• Efficacy: Objective response rate(ORR) [Срок оценки: up to 26 cycles (there are 28 days for each cycle)]

Критерии участия

• phase I: dose escalation phase

Критерии включения

• Patient has ability to understand the risks of the study and is willing to comply with the protocol and has signed a written informed consent.
• Aged 18-70 years (inclusive), males and females.
• Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative do not exist or are no longer effective.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Expected life expectancy ≥ 12 weeks
• Recovered from toxicities of prior therapy to Grade 0 or 1
• An adequate renal, liver and bone marrow function.

Критерии исключения

• History of another primary malignancy within 2 years prior to Day 1, except for adequately treated basaloma, in situ cancer, or other cancers whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the current study.
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1.
• Treatment with radiation therapy, chemotherapy, biotherapy, targeted therapies or hormones within 4 weeks prior to Day 1.
• Receiving investigational therapy within 4 weeks prior to Day 1.
• Concomitant use of repaglinide, medium/strong CYP2C8/CYP2B6/ CYP2C9 inhibitors/inducers.
• Pleural effusion or ascites which need to be drained every other week or more frequently.
• HBV infection and HBV-DNA ≥ 2,000 IU/mL
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• History of human immunodeficiency virus (HIV) infection or syphilis infection.
• History of cardiac disease fits any of the following conditions：

• NYHA III or IV CHF；
• QTcF : male > 450ms，female > 470ms；
• Myocardial infarction, bypass surgery, stent surgery within 6 months prior to Day 1；
• Other cardiac disease that the investigator judged unsuitable for inclusion.
• Females who are pregnant or breast-feeding
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
• Previously allergic to ethanol, polyoxyethylene (35) castor oil, N, N-dimethylacetamide.
• Unwillingness or inability to comply with the study protocol for any reason

• phase II: pancreatic cancer

Критерии включения

• Patient has ability to understand the risks of the study and is willing to comply with the protocol and has signed a written informed consent.
• Aged 18-70 years (inclusive), males and females.
• Histologically or cytologically confirmed pancreatic cancer that is unresectable or cannot be controlled by local treatment and for which standard curative do not exist or are no longer effective.
• At least one measurable lesion that meets RECIST 1.1 criteria.
• Can provide pathological wax blocks or sections (including archived pathological wax blocks or sections) for AKR1C3 expression analysis and be confirmed that AKR1C3 expression is strongly positive.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Expected life expectancy ≥ 12 weeks
• Recovered from toxicities of prior therapy to Grade 0 or 1
• An adequate renal, liver and bone marrow function.

Критерии исключения

• History of another primary malignancy within 2 years prior to Day 1, except for adequately treated basaloma, in situ cancer, or other cancers whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the current study.
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1.
• Treatment with radiation therapy, chemotherapy, biotherapy, targeted therapies or hormones within 4 weeks prior to Day 1.
• Receiving investigational therapy within 4 weeks prior to Day 1.
• Concomitant use of repaglinide, medium/strong CYP2C8/CYP2B6/ CYP2C9 inhibitors/inducers.
• Pleural effusion or ascites which need to be drained every other week or more frequently.
• HBV infection and HBV-DNA ≥ 2,000 IU/mL
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• History of human immunodeficiency virus (HIV) infection or syphilis infection.
• History of cardiac disease fits any of the following conditions：

• NYHA III or IV CHF；
• QTcF : male > 450ms，female > 470ms；
• Myocardial infarction, bypass surgery, stent surgery within 6 months prior to Day 1；
• Other cardiac disease that the investigator judged unsuitable for inclusion.
• Females who are pregnant or breast-feeding
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
• Previously allergic to ethanol, polyoxyethylene (35) castor oil, N, N-dimethylacetamide.
• Unwillingness or inability to comply with the study protocol for any reason

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

• Jinlin Cancer Hospital — Changchun

Идентификаторы

NCT: NCT06245330 · AT-001-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗