Autologous Neoantigen-Specific T-Cell Therapy for Advanced Hepatocellular Carcinoma

NCT07123545 | Recruiting Phase 1

• 1 other identifier: ZY-INEO-T01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this open-label, single-arm phase I/II clinical trial is to evaluate the feasibility, safety, and anti-tumor efficacy of the autologous neoantigen-specific T-cell therapy (iNeo-Vac-T01) in patients with advanced hepatocellular carcinoma who have failed second-line or later systemic therapies.

Conditions

Advanced Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (2)

• Successful Administration Rate of iNeo-Vac-T01

  Proportion of enrolled patients who received the complete planned iNeo-Vac-T01 cell infusion.

  Up to 3 years

• Incidence of Adverse Events (AEs)

  Incidence of adverse events (AEs) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, including serious adverse events (SAEs) .

  Up to 3 years

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  up to 3 years

• Objective Response Rate (ORR)

  up to 3 years

• Neoantigen-Specific T Cell Response in Peripheral Blood

  up to 3 years

Study Arms (1)

Experimental group（iNeo-Vac-P01+iNeo-Vac-T01）

EXPERIMENTAL

iNeo-Vac-P01 Personalized Neoantigen Peptide Vaccine Route of administration: Subcutaneous injection. Dosage: 0.3 mg per peptide. Administration schedule: Days 1, 4, 8, 15, 22, 52, and 82 (relative to treatment initiation). iNeo-Vac-T01 Personalized Cell Therapy (initiated at Week 9) Route of administration: Intravenous infusion. Dosing regimen: "3+3" dose escalation design. Dose Level 1: 5 × 10⁹ to 10 × 10⁹ cells. Dose Level 2: 1 × 10¹⁰ to 5 × 10¹⁰ cells. Lymphodepleting preconditioning regimen: Agents: Cyclophosphamide + Fludarabine. Timing: Administered prior to cell infusion. Post-infusion supportive therapy: Interleukin-2 (IL-2) support for 10 days.

Biological: iNeo-Vac-P01 Personalized Neoantigen Peptide Vaccine; Biological: iNeo-Vac-T01 Personalized T Cell Injection

Interventions

iNeo-Vac-P01 Personalized Neoantigen Peptide Vaccine BIOLOGICAL

Administered subcutaneously at 0.3 mg/peptide on Days 1, 4, 8, 15, 22, 52, and 82, followed by booster immunizations every 2-3 months.

Experimental group（iNeo-Vac-P01+iNeo-Vac-T01）

iNeo-Vac-T01 Personalized T Cell Injection BIOLOGICAL

Administered via intravenous infusion: Dose Level 1: 5×10⁹ to 10×10⁹ cells; Dose Level 2: 1×10¹⁰ to 5×10¹⁰ cells.

Experimental group（iNeo-Vac-P01+iNeo-Vac-T01）

Eligibility Criteria

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

You may qualify if:

• Aged 18 to 75 years (inclusive)
• Histologically confirmed advanced hepatocellular carcinoma (HCC) with:
• <!-- -->
• Radiologically measurable disease per RECIST v1.1
• Documented progression on ≥2 prior lines of systemic therapy 3.Life expectancy ≥6 months 4.ECOG performance status 0 or 1 5.Available archival or fresh tumor tissue sufficient for comprehensive genomic profiling OR existing whole-genome sequencing (WGS), whole-exome sequencing (WES), or RNA-sequencing data meeting prespecified quality thresholds 6.Adequate organ and marrow function:
• (1)Hematologic:
• White blood cell count (WBC) ≥3.0 × 10⁹/L
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
• Hemoglobin ≥9.0 g/dL (≥5.6 mmol/L)
• Platelet count ≥100 × 10⁹/L (2)Hepatic:
• a.Total bilirubin ≤1.5 × upper limit of normal (ULN) (≤3 × ULN if liver metastases present) b.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN (≤5 × ULN if liver metastases present) (3)Renal:
• Serum creatinine ≤1.5 × ULN OR
• Calculated creatinine clearance (CrCl) ≥50 mL/min (Cockcroft-Gault formula) (4)Coagulation:
• <!-- -->
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN AND activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless receiving therapeutic anticoagulation with stable INR/PT/aPTT within target range) 7.Reproductive Status:

You may not qualify if:

• History of other active malignancies within the past 5 years, except:
• Adequately treated basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix
• Other malignancies considered cured with minimal risk of recurrence (e.g., localized thyroid cancer) 2.Failure to identify therapeutically targetable neoantigens via genomic analysis 3.Prior allogeneic bone marrow, solid organ, or hematopoietic stem cell transplantation 4.Active or symptomatic central nervous system (CNS) metastases except:
• (1)Previously treated CNS metastases that are radiologically stable (no evidence of progression) for ≥4 weeks and (2)Asymptomatic and off corticosteroid/anticonvulsant therapy for ≥4 weeks prior to enrollment (3)Note: Leptomeningeal disease is excluded regardless of stability or treatment status.
• Active bacterial, fungal, or mycobacterial infection requiring systemic therapy (including untreated latent tuberculosis) 6.Active viral infections meeting any of the following:
• Detectable HBV DNA (if HBsAg positive or HBcAb positive)
• Detectable HCV RNA
• HIV infection (serologically confirmed)
• Active syphilis infection (serologically confirmed) 7.Active autoimmune disease requiring systemic immunosuppressive therapy (\>10 mg prednisone equivalent daily) within the past 2 years, except:
• <!-- -->
• Vitiligo
• Type 1 diabetes mellitus
• Hypothyroidism stable on hormone replacement
• Psoriasis not requiring systemic therapy 8.Systemic immunosuppressive therapy (\>10 mg prednisone equivalent per day) within 14 days prior to planned cell infusion (topical, inhaled, or ophthalmic corticosteroids are permitted) 9.Uncontrolled intercurrent illness including, but not limited to:

Sponsors & Collaborators

• Zhejiang University: lead
• Hangzhou Neoantigen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Central Study Contacts

Tingbo Liang

CONTACT

+8619941463683; liangtingbo@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director physician

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 14, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2029
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)