An Open-label Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of CREPT-618 in Patients With Locally Advanced Hepatocellular Carcinoma
This is a single-center, open-label, dose-escalation Phase I clinical study designed to evaluate the safety (incidence of adverse events), maximum tolerated dose (MTD), optimal biological dose (OBD), and recommended Phase II dose (RP2D) of CREPT-618 in adult patients aged 18-75 with locally advanced hepatocellular carcinoma who have failed standard treatment. The study adopts a 3+3 dose escalation design for dose climbing, primarily consisting of three dose groups: low dose, medium dose, and high dose. Patient enrollment and dose escalation in each group will be based on safety evaluation results. Pharmacokinetic parameters and preliminary efficacy indicators will also be assessed.
• Age: 18-75 years old.
• Diagnosis: Patients with histologically confirmed locally or advanced hepatocellular carcinoma (HCC) (BCLC stage C or ineligible for curative treatment).
• Hepatitis B Status: Inactive hepatitis B virus infection with negative HBV-DNA viral load.
• Informed Consent: Ability to understand and voluntarily sign the informed consent form.
• Prior Treatment: Failed prior standard treatment.
• ECOG Performance Status: ECOG performance status score of 0-2.
• Measurable Disease: Presence of at least one measurable lesion according to RECIST 1.1 criteria.
• Biomarker Status: Must be able to provide at least six unstained slides for testing, confirming both CREPT and ASGPR receptor positivity in liver cancer tissue. Alternatively, a tumor biopsy can be performed to confirm CREPT and ASGPR double positivity. H-score must be greater than 50% with a staining intensity of 2+.
• Organ Function: Acceptable major organ function as defined by the following laboratory values: Platelets ≥ 70 × 10\^9/L Neutrophils ≥ 1.5 × 10\^9/L Hemoglobin ≥ 90 g/L Prothrombin time prolongation ≤ 6 seconds Renal function: Creatinine clearance (Ccr) \> 50 ml/min (calculated using the Cockcroft-Gault formula).
• Life Expectancy: Expected life expectancy of at least 3 months.
• Contraception: Male and female patients of childbearing potential must agree to use effective contraception (hormonal, barrier, or abstinence) during the study and for at least 6 months after the last dose of the study drug. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment.
• Compliance: Patients must be compliant and willing to adhere to follow-up procedures.