Study of AU409 Capsule in Advanced Hepatocellular Carcinoma Patients Who Failed Standard Treatment

NCT06374485 | Recruiting Phase 1

• 1 other identifier: AU409-LEES-2021-03
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase I, dose-escalation study of AU409 in advanced hepatocellular carcinoma patients who failed standard treatment. A '3+3' dose-escalation design will be utilized to gradually increase the dose of AU409, aiming to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor efficacy of multi-dose AU409 in patients with advanced HCC.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity

  To determine the maximum tolerated dose (MTD) and the recommended phase II dose (R2PD).

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (7)

• Maximum Tolerated Dose

  Through study completion, an average of 2 years

• Recommended Phase 2 Dose

  Through study completion, an average of 2 years

• Objective Response Rate

  Through study completion, an average of 2 years

• Disease Control Rate

  Through study completion, an average of 2 years

• Duration of Response

  Through study completion, an average of 2 years

Study Arms (3)

AU409 120mg QD

EXPERIMENTAL

Cohort 1

Drug: AU409

AU409 210mg QD

EXPERIMENTAL

Cohort 2

Drug: AU409

AU409 300mg QD

EXPERIMENTAL

Cohort 3

Drug: AU409

Interventions

AU409 DRUG

Oral administration

AU409 120mg QD; AU409 210mg QD; AU409 300mg QD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female of 18-75 (inclusive) years of age.
• Patients with histologically and/or cytologically and/or radiologically confirmed advanced (unresectable or metastatic) hepatocellular carcinoma (HCC) that have failed any of standard treatment (including Immunotherapies and/or Tyrosine Kinase Inhibitor therapies, or Oxaliplatin-based systemic chemotherapies), recurrence, or are intolerant.
• Before treatment initiation, patients must have previously completed chemotherapy, radiotherapy, interventional therapy for more than 4 weeks (except palliative radiotherapy for bone metastasis). And all treatment-related toxicities (except hair loss, pigmentation, and chemotherapy-related neurotoxicities, etc.) have recovered (≤ level 1 or baseline level).
• Have at least one evaluable disease lesion based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST).
• ECOG score of 0 or 1.
• Patients with Child Pugh class A or some class B (≤7 and no hepatic encephalopathy).
• Have a life expectancy of \>12 weeks.
• Able to be orally administered.
• Laboratory examinations must meet the following criteria within 7 days before treatment initiation:
• Absolute neutrophil count（ANC）≥1.5 × 109/L，platelets（PLT） count ≥75 × 109/L，hemoglobin（HGB）≥90 g/L，and patients are not allowed to receive blood transfusion or other haematopoietic growth factors within 14 days before treatment initiation.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be ≤5.0×upper limit of normal (ULN).
• Total bilirubin (TBIL) ≤1.5×ULN.
• Ablumin (ALB) ≥28g/L.
• Serum creatinine (CRE) ≤1.0×ULN, creatinine clearance rate (CCR) ≥60 mL/min (Cockcroft-Gault equation).
• International normalized ratio（INR）≤1.5，prothrombin time (PT) ≤1.5×ULN.

You may not qualify if:

• Patients of central nervous system metastasis with clinical symptoms (except patients who are asymptomatic, and no disease progression confirmed by MRI diagnosis for more than 28 days).
• Allergies to any ingredients or excipients in AU409.
• Treatment with other anticancer therapies (including surgery, radiation therapy, chemotherapy, anti-angiogenic therapy, targeted therapy, or radiofrequency ablation therapy, etc.) or investigational therapy (except patients who stop treatment of Chinese patent medicine or Chinese herbal medicine for more than 7 days, or complete palliative radiotherapy for bone metastasis \>2 weeks) within 28 days prior to the first dosing.
• QTc ≥470 msec during screening period (Fridericia's equation) or with a history of congenital long QT syndrome.
• Patients with history of gastrointestinal surgery that may change the absorption and activity of drugs in their body (such as total gastrectomy, small bowel resection, external bile shunt, etc.) in combination with refractory hiccups, nausea, vomiting, and other diseases that affect drug absorption (such as peptic ulcer, inflammatory bowel disease, lactose intolerance, malabsorption syndrome or chronic diarrhea, etc.).
• Patients who require serous effusion for continuous drainage or drug infusion (such as ascites, pleural effusion, etc.), or have undergone portal vein shunt.
• Patients with gastrointestinal perforation and/or fistula, abdominal abscess, visceral fistula, intestinal obstruction, hepatic encephalopathy, portal vein and inferior vena cava cancer thrombus within 3 months prior to the treatment initiation.
• Patients have gastrointestinal bleeding (including esophageal or gastric varices, local active ulcer lesions, etc.), or have a clear bleeding tendency, or are receiving anticoagulation/thrombolytic therapy within 3 months before treatment initiation. Positive result of occult blood needs to identifythe causes.
• Patients with interstitial lung disease, non-infectious pneumonia.
• History of allogeneic stem cell transplantation or organ transplantation.
• Patients who receive major surgery (except biopsy and puncture) or with major trauma within 28 days before treatment initiation.
• Patients with infectious diseases that affect daily activities or require systemic treatment (such as the use of hormones, antibiotics, antifungal drugs, antiviral drugs, and oxygen inhalation), including but not limited to infections requiring hospitalization, bacteremia, severe pneumonia, etc.
• Uncontrolled diseases, including a) New York Heart Association (NYHA) Class II or higher heart failure, b) Severe/unstable angina pectoris, c) Primary cardiomyopathy, d) Myocardial infarction or coronary/peripheral artery bypass surgery occurred within 6 months before treatment initiation, e) Uncontrollable high blood pressure, f) Severe arrhythmia requiring medication or intervention, g) Echocardiographic left ventricular ejection fraction \<50% during the screening period, h) Deep vein thrombosis/arterial thrombosis /Pulmonary vein embolism occurred within 2 months before treatment initiation, i) Cerebrovascular accident or transient ischemic attack occurred within 6 months before treatment initiation, j) Ocular lens disease (such as cataract), k) Diabetes that has not been effectively controlled, l) Thyroid diseases that have not been effectively controlled, m) Urine protein≥2+ and quantity of 24-hour urine protein ≥1.0g.
• Human immunodeficiency virus infection (HIV 1/2 antibody positive).
• HBV infection (HBsAg positive and HBV DNA ≥2000 IU/mL); Hepatitis C virus (HCV) antibody is positive and HCV RNA\>103 copies/ml; HBsAg and HCV antibodies are both positive.

Sponsors & Collaborators

• Lee's Pharmaceutical Limited: lead

Study Sites (1)

Department of Clinical Oncology, Queen Mary Hospital

Hong Kong, China

RECRUITING

Central Study Contacts

Chi Leung Chiang

CONTACT

+852 22554352; chiangcl@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: April 18, 2024
• Study Start: May 21, 2024
• Primary Completion: December 28, 2025
• Study Completion: December 31, 2025
• Last Updated: August 26, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)