Phase IIb Study of AST-3424 in Patients With AKR1C3-high Expressing Advanced Hepatocellular Carcinoma

NCT ID: NCT07310173

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2027-12-01

Brief Summary

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The goal of this clinical trial is to learn if drug AST-3424 works to treat AKR1C3 high expressing advanced hepatocellular carcinoma after failure of systemic therapy with immune checkpoint inhibitors. The main question it aims to answer is:

Does AST-3424 prolong survival in patients with AKR1C3-high Expressing advanced Hepatocellular Carcinoma who have progressed after immune checkpoint inhibitors based therapies?

Researchers will compare AST-3424 to regorafenib (current optional therapy for target patients) to see if AST-3424 works.

Participants will:

Receive AST-3424 infusion on Day 1 and Day 8 of each 21-day treatment cycle or take regorafenib once a day on Day 1 -Day 21 of each 28-day treatment cycle.

Detailed Description

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Conditions

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HCC - Hepatocellular Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AST3424, 4mg/m^2

Group Type EXPERIMENTAL

AST-3424

Intervention Type DRUG

AST-3424 is administered via intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle

AST3424, 6mg/m^2

Group Type EXPERIMENTAL

AST-3424

Intervention Type DRUG

AST-3424 is administered via intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle

regorafenib

Group Type ACTIVE_COMPARATOR

Regorafenib Tablets

Intervention Type DRUG

160 mg orally, once daily for the first 21 days of each 28-day treatment cycle.

Interventions

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AST-3424

AST-3424 is administered via intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle

Intervention Type DRUG

Regorafenib Tablets

160 mg orally, once daily for the first 21 days of each 28-day treatment cycle.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients with pathologically confirmed advanced hepatocellular carcinoma (HCC).
2. Documented disease progression confirmed by medical imaging after failure of prior systemic therapy regimens containing immune checkpoint inhibitors (ICIs).
3. Barcelona Clinic Liver Cancer (BCLC) stage B or C; ineligible for or refusing surgical resection or locoregional liver therapies (including transarterial intervention and ablation).
4. Child-Pugh class A or B liver function (score ≤ 7), with no history of hepatic encephalopathy.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
6. At least one measurable extracranial lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
7. Expected survival ≥ 3 months.
8. Availability of pathological tissue blocks or sections (including archived samples) for AKR1C3 expression and related biomarker analysis. Immunohistochemistry (IHC) results must confirm high expression of AKR1C3.
9. Adequate organ function.
10. For subjects positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb):

HBV DNA level must be \< 2000 IU/mL or 10⁴ copies/mL Subjects must be receiving anti-HBV therapy . This therapy must be maintained throughout the study period and for 6 months after the last dose of study drug.

For subjects positive for HCV antibody, HCV-RNA level must be below the lower limit of detection (LLOD) of the study center.
11. Female subjects of childbearing potential must be non-lactating and have a negative pregnancy test result within 7 days prior to treatment initiation. A positive urine pregnancy test result must be confirmed by a serum pregnancy test.
12. Female and male subjects of childbearing potential must agree to use effective contraceptive measures from the time of study enrollment until 6 months after the last dose of study drug.
13. Subjects must voluntarily participate in the study, provide written informed consent after a full understanding of the study details, and have good compliance to cooperate with study treatment, observation, and follow-up procedures.

Exclusion Criteria

1. Patients with intrahepatic cholangiocarcinoma, dual-phenotype hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, or carcinosarcoma.
2. Untreated active central nervous system (CNS) metastases. Subjects with CNS metastases who have received adequate treatment, achieved stable disease for at least 4 weeks confirmed by clinical examination and brain MRI during screening, require no steroid or anticonvulsant therapy, and present no clinical symptoms may be enrolled in the study.
3. A history of other malignant tumors within 2 years, except for adequately treated basal cell carcinoma of the skin, carcinoma in situ of the lung, breast, or other sites, or other tumors whose related treatments will not interfere with the safety or efficacy evaluation of the study drug.
4. A history of severe cardiovascular and cerebrovascular diseases.
5. Has received anti-tumor therapies including locoregional radiotherapy, chemotherapy, immunotherapy, or targeted therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose; for treatment with nitrosourea or mitomycin C, a 6-week washout period is required; for oral fluoropyrimidine drugs or small-molecule targeted therapy drugs, only a 2-week washout period is needed.
6. Has received major surgery other than diagnostic procedures or locoregional therapy targeting liver lesions within 4 weeks prior to the first dose.
7. Has received investigational drugs in other clinical trials within 4 weeks prior to the first dose.
8. All toxicities from prior anti-cancer therapies must have resolved to ≤ grade 1 at the start of study drug administration.
9. Moderate to large symptomatic pleural effusion, pericardial effusion, or ascites requiring thoracentesis/paracentesis or with a history of thoracentesis/paracentesis within 2 weeks prior to the start of study treatment. .
10. Need for concomitant use of strong CYP3A4 inhibitors or inducers during the study period.
11. Any severe acute or chronic infections requiring systemic antibiotic or antiviral therapy at screening.
12. Known human immunodeficiency virus (HIV) infection or positive syphilis test result.
13. Pregnant, lactating, or women planning to become pregnant.
14. Concomitant diseases that may interfere with the conduct of the study, or physical abnormalities that the investigator deems pose an excessive risk to the subject, including but not limited to a history of significant gastrointestinal bleeding within 3 months prior to enrollment or a high risk of bleeding, active peptic ulcer, uncontrolled mental illness, or mental disorders that may interfere with the subject's understanding of the informed consent form or cooperation with treatment.
15. A history of hypersensitivity to ethanol or propylene glycol.
16. Other reasons judged by the investigator that make the subject unsuitable for participation in this clinical study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zhejiang Hisun Pharmaceutical Co. Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Nanjing Tianyinshan Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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WEI QU

Role: CONTACT

Phone: 8618067913551

Email: [email protected]

Facility Contacts

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Chen Xun

Role: primary

Other Identifiers

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HSE001-Ⅱ-01

Identifier Type: -

Identifier Source: org_study_id