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

Ascentawits Pharmaceuticals

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Solid Tumor

Pancreatic Cancer

Treatments

Drug: AST-001

Study type

Interventional

Funder types

Industry

Identifiers

NCT06245330

AT-001-001

Details and patient eligibility

About

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.

Enrollment

180 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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：
1. NYHA III or IV CHF；
2. QTcF : male > 450ms，female > 470ms；
3. Myocardial infarction, bypass surgery, stent surgery within 6 months prior to Day 1；
4. 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：
1. NYHA III or IV CHF；
2. QTcF : male > 450ms，female > 470ms；
3. Myocardial infarction, bypass surgery, stent surgery within 6 months prior to Day 1；
4. 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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

180 participants in 2 patient groups

Dose escalation phase

Experimental group

Description:

AST-001 (5.0 mg/m\^2 to 40.0 mg/m\^2) will be administered by IV infusion on Days 1, 8 and 15 of each 28-day cycle to determine the MTD and RP2D with a BOIN design.

Treatment:

Drug: AST-001

phase II pancreatic cancer

Experimental group

Description:

AST-001 (RP2D) will be administered by IV infusion on Days 1, 8 and 15 of each 28-day cycle

Treatment:

Drug: AST-001