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

Official title

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

Overview

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.

Interventions

• Drug AST-001
  liquid formulation for Intravenous infusion

Primary outcome measures

• Incidence and severity of adverse events (AEs) [Time frame: 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) [Time frame: Day 1 of each cycle(there are 26 cycles; 28 days for each cycle)]
• Assess safety changes of body weight. [Time frame: pre-AST-001 infusion of each cycle (there are 26 cycles; 28 days for each cycle)]
• Number of participants with dose limiting toxicities (DLTs) [Time frame: Throughout Cycle 1 (28 days for each cycle)]
• Define the Recommended Phase 2 Dose (RP2D) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: up to 26 cycles (there are 28 days for each cycle)]

Eligibility criteria

• phase I: dose escalation phase

Inclusion criteria

• 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.

Exclusion criteria

• 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

Inclusion criteria

• 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.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Jinlin Cancer Hospital — Changchun

Identifiers

NCT: NCT06245330 · AT-001-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗