Patients with advanced hepatocellular carcinoma with high expression of AKR1C3
Conditions
Interventions
Experimental Group:AST3424 injection
Control group:Regorafenib Tablets
Sponsors
Nanjing Tianyi Mountain Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Male or female, aged 18 to 75 years. 2.Diagnosed with advanced hepatocellular carcinoma (HCC) confirmed by histopathological examination. 3.Failed prior treatment regimens containing immune checkpoint inhibitors, including PD-1 monoclonal antibody monotherapy, targeted-immunotherapy combination (molecular targeted drugs combined with PD-1/PD-L1 monoclonal antibodies), or dual-immunotherapy combination (PD-1/PD-L1 monoclonal antibodies combined with CTLA-4 monoclonal antibodies), with confirmed disease progression by medical imaging. Note: Disease progression after prior immunotherapy-based regimens is defined as having received treatment with immune checkpoint inhibitors for >= 2 months, with treatment failure, disease progression during treatment, or recurrence within 6 months after completion of adjuvant therapy. 4.Barcelona Clinic Liver Cancer (BCLC) stage B or BCLC stage C, unsuitable for or refusing surgical resection or locoregional liver treatments (including transarterial intervention and ablation therapy). 5.Child-Pugh liver function classification A or better B (= 3 months. 9.Capable of providing formalin-fixed paraffin-embedded (FFPE) tissue blocks or slides (including archived pathological blocks and sections) for AKR1C3 expression and related biomarker analysis, with immunohistochemistry results confirming that tumor cells with staining intensity of 2+ and/or 3+ account for >= 70%. 10.Major organ functions must meet the following requirements: no blood transfusions, use of hematopoietic growth factors, or administration of human albumin within 14 days prior to screening: (1) Hemoglobin (Hb) >= 90g/L (2) Platelet count (BPC) >= 80 × 10^9/L (3) Absolute neutrophil count (ANC) >= 1.5 × 10^9/L (4) Serum total bilirubin (BIL) = 29g/L (8) Serum creatinine (SCr) 50mL/min (9) Left Ventricular Ejection Fraction (LVEF) >= 50% (10) For males, Fridericia method-corrected QT interval (QTcF) < 450ms; for females, QTcF < 470ms 11.For subjects with positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb), HBV DNA must be < 2000 IU/mL or 104 copies/mL, and antiviral therapy with entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, amenamevir, or premafivir must be administered according to the national "Guidelines for the Prevention and Treatment of Chronic Hepatitis B". This treatment must be maintained throughout the study and continued for 6 months after the last dose. For HCV antibody-positive subjects, HCV-RNA must be below the lower limit of detection at the study center. 12.Female subjects of childbearing potential must have a negative pregnancy test (urine pregnancy test) within 7 days prior to initiation of treatment (a positive urine pregnancy test must be confirmed by serum pregnancy test) and mu
Exclusion criteria
Exclusion criteria: 1. Hepatocellular carcinoma, biphenotypic liver cancer, fibroblastic platelet-like hepatocellular carcinoma, and carcinosarcoma. 2. Untreated active central nervous system (CNS) metastasis. If the CNS metastasis of the subject has been adequately treated and is confirmed to be stable for at least 4 weeks during the screening period through clinical examination and brain MRI, without the need for steroid or anticonvulsant drugs and without clinical symptoms, they can participate in this study. 3. History of other malignant tumors within 2 years, except for fully treated skin basal cell carcinoma, lung, breast and other site in situ carcinomas, or other tumors that do not interfere with the safety or efficacy evaluation of the current study drug. 4. Severe cardiovascular and cerebrovascular diseases history, including but not limited to: (1) Severe cardiac rhythm or conduction abnormalities, such as clinically intervened ventricular arrhythmias, II-III degree atrioventricular block, etc.; (2) Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or above cardiovascular and cerebrovascular events within 6 months before the first administration; (3) NYHA cardiac function classification >= III grade; (4) Uncontrolled clinical hypertension (systolic pressure >=160mmHg or diastolic pressure >= 100mmHg). 5. Received anti-tumor treatment such as local radiotherapy, chemotherapy, immunotherapy and targeted therapy within 4 weeks or 5 half-lives before the first administration; if treated with nitrosourea or mitomycin C, a 6-week washout period is required; if taking oral fluorouracil drugs or small molecule targeted therapy drugs, a 2-week washout period is sufficient. 6. Within 4 weeks before the first administration, undergone major surgery other than diagnostic procedures and local treatment for liver lesions, including but not limited to local radiotherapy, physical and chemical ablation, transcatheter hepatic arterial chemotherapy embolization (TACE) and continuous hepatic artery perfusion chemotherapy (HAIC). If the washout period for local treatment is less than 4 weeks, but after strict review by the principal investigator of the leading unit, it is determined not to affect the safety and efficacy evaluation of the study drug, such as alopecia, grade 2 peripheral neuropathy, stable thyroid function due to hormone replacement therapy, etc. can be enrolled. 7. Within 4 weeks before the first administration, used other anti-tumor clinical trial drugs, such as marketed or drugs with known half-life trial drugs, the washout period can refer to exclusion criteria 5. 8. At the time of starting to use the study drug, all toxicities of previous anti-cancer treatment should have recovered to <= grade 1, except for toxicities without safety risks as judged by the main investigator of the research center, such as hair loss, grade 2 peripheral neuropathy, stable hypothyroidism due to hormone replacement therapy, etc. 9. Have clinical symptoms of significant pleural effusion, pericardial effusion or abdominal effusion, requiring puncture and drainage, or have undergone puncture and drainage within 2 weeks before the start of the study treatment, only those with medical imaging showing a small amount of effusion but without clinical symptoms can be included. 10. During the study period, it is necessary to combine the use of potent CYP3A4 inhibitors or inducers. 11. Need to use systemic antibiotics (antibacterial,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 9-month OS rate;Observation results related to safety, such as adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy evaluation (PFS?ORR?DCR?DOR?TTP?TTR); | — |
Countries
China
Contacts
Public ContactChen Xun
Nanjing Tianyi Mountain Hospital
Outcome results
None listed