A Phase I Study of CREPT-618 in Locally Advanced HCC

NCT07364357 | Recruiting Phase 1

• 1 other identifier: HY-618-IIT01
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• Primary Objective

  Safety: Incidence of adverse events (AEs) (graded according to CTCAE v5.0)， Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)

  From enrollment to the end of treatment at 12 weeks

Secondary Outcomes (10)

• Pharmacokinetics (PK)

  baseline and after treatment (0.5h, 1h, 2h, 4h, 8h, 24h for first dose, 1h for second dose(day15) and third dose(day 29))

• Pharmacokinetics (PK)

  baseline and after treatment (0.5h, 1h, 2h, 4h, 8h, 24h for first dose, 1h for second dose(day15) and third dose(day 29))

• Pharmacokinetics (PK)

  baseline and after treatment (0.5h, 1h, 2h, 4h, 8h, 24h for first dose, 1h for second dose(day15) and third dose(day 29))

• Pharmacodynamics(PD)

  baseline and 6 weeks after treatment

• Preliminary Efficacy

  about 2 years

Other Outcomes (1)

• Biomarker analysis

  Baseline and 6 weeks after treatment

Study Arms (1)

CREPT-618

EXPERIMENTAL

The study employs a 3+3 dose escalation design for dose titration, consisting of three primary dose groups: low dose(sentinel dose), medium dose, and high dose.Starting with the sentinel dose, one sentinel patient will be enrolled in the low-dose group and observed for up to 28 days. If no dose-limiting toxicity (DLT) occurs in the sentinel patient, enrollment will proceed. To ensure the trial can escalate to the anticipated effective dose, if no DLTs are observed in the low-, medium-, or high-dose groups, and no changes are observed in objective response rate or liver function indicators, the dose may be adjusted to a new dose.

Genetic: gene therapy

Interventions

gene therapy GENETIC

Using small nucleic acid drug to targeting CREPT

CREPT-618

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• \- Prior Treatment:
• a) Received systemic anti-tumor therapy (chemotherapy, radiotherapy, biological therapy, cytokine therapy, immunotherapy) or participated in other therapeutic clinical studies within 4 weeks prior to the first dose of the study drug. This includes nitrosourea drugs or mitomycin C within 6 weeks prior to the first dose. Exceptions: i) Oral fluoropyrimidine drugs or small molecule targeted agents received more than 2 weeks or 5 half-lives before the first dose (whichever is longer, but not exceeding 28 days).
• ii) Traditional Chinese medicine for anti-tumor treatment received more than 2 weeks prior to the first dose.
• iii) Palliative bone-directed radiotherapy. b) Planned to undergo major surgery within 28 days before the start of the study treatment (diagnostic biopsies are permitted).
• c) Received systemic immunostimulants within 4 weeks or 5 half-lives (whichever is longer) prior to enrollment.
• d) Used systemic corticosteroids (prednisone \> 10 mg/d or equivalent dose) or other immunosuppressive drugs within 14 days before the start of study treatment. Exceptions include topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids, or short-term use of corticosteroids for prophylactic purposes.
• Autoimmune Disease: Active autoimmune disease or a history of autoimmune disease within the past 2 years. Exceptions: vitiligo, Graves' disease, Hashimoto's disease, or psoriasis that did not require systemic treatment within the past 2 years.
• Severe Liver Decompensation: Presence of any of the following symptoms or abnormal indicators of severe liver function decompensation: Refractory ascites (unresponsive to diuretics or requiring frequent paracentesis); Hepatic encephalopathy ≥ Grade 2 (West Haven criteria); History of or current spontaneous bacterial peritonitis (SBP);Hepatorenal syndrome; History of esophagogastric variceal bleeding (within the last 3 months); Hepatic hydrothorax, hepatopulmonary syndrome, portal vein thrombosis (complete occlusion), or other severe liver-related complications;
• Laboratory Values: Total bilirubin \> 3 mg/dL (51.3 μmol/L) Albumin \< 2.8 g/dL (28 g/L) INR \> 2.3 or prothrombin time prolongation \> 6 seconds ALT or AST \> 3 times the upper limit of normal (ALT \> 120 U/L, AST \> 105 U/L) Serum sodium \< 130 mmol/L Serum creatinine \> 1.5 mg/dL (133 μmol/L);
• Severe Infection/Comorbidities:
• Positive for HIV or a known history of AIDS.
• Positive for Hepatitis C virus (anti-HCV or HCV-RNA). (Patients with Hepatitis B may be included if they are receiving and willing to continue antiviral treatment according to local guidelines).
• Interstitial lung disease, obstructive lung disease, active bronchospasm, or oxygen saturation \< 93% ("pulmonary insufficiency"), or any other active or severe pulmonary disease that may cause severe respiratory distress.
• Unresolved Toxicity: Unresolved toxicities from prior anti-cancer treatment that have not recovered to ≤ Grade 1. Exceptions may include toxicities judged by the investigator to not pose a safety risk (e.g., alopecia, Grade 2 peripheral neuropathy, or stable hypothyroidism on hormone replacement therapy).
• Comorbidities: Uncontrolled diabetes (fasting blood glucose \> 200 mg/dL or 11.1 mmol/L), severe cardiovascular disease (e.g., myocardial infarction within the last 6 months, unstable angina, NYHA Class III-IV heart failure), etc.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Genetic Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Engineering; Genetic Techniques; Investigative Techniques

Study Officials

• Ning Li, M.D.

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peiwen Ma, M.D.

CONTACT

+86010-87788165; mapeiwen@cicams.ac.cn

Study Design

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

Study Record Dates

• First Submitted: September 16, 2025
• First Posted: January 23, 2026
• Study Start: September 15, 2025
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): September 15, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)