Autologous neoantigen T-cell therapy for advanced liver cancer

Feasibility, Safety and Efficacy Study of Autologous Neoantigen-Specific T-Cell Therapy (iNeo-Vac-T01) in Advanced Hepatocellular Carcinoma Patients

This treatment tries a personalized neoantigen-specific T-cell therapy for people with advanced hepatocellular carcinoma who have not responded to two or more systemic treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: immunotherapy, prednisone
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07123545 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm Phase 1/2 trial testing a personalized approach that combines a neoantigen peptide vaccine (iNeo-Vac-P01) and autologous neoantigen-specific T-cell infusion (iNeo-Vac-T01). Patients' tumor tissue or existing genomic data are used to identify tumor-specific neoantigens and manufacture individualized peptides and T cells. The study enrolls adults with measurable advanced HCC who progressed after at least two prior systemic therapies and have adequate organ function and ECOG 0–1. Primary goals are to determine feasibility, safety, and signs of anti-tumor activity from the personalized T-cell product.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 years with histologically confirmed advanced HCC, measurable disease by RECIST v1.1, documented progression after ≥2 systemic therapies, ECOG 0–1, life expectancy ≥6 months, adequate organ function, and available tumor tissue or qualifying sequencing data.

Not a fit: Patients with poor organ or marrow function, ECOG performance >1, insufficient tumor tissue or sequencing data, or rapidly declining clinical status are unlikely to benefit from this personalized manufacturing-dependent therapy.

Why it matters

Potential benefit: If successful, this personalized therapy could shrink tumors or slow disease progression for some patients who have exhausted standard treatment options.

How similar studies have performed: Neoantigen vaccines and adoptive T-cell therapies have shown promising signals in melanoma and some solid tumors, but neoantigen-specific T-cell therapy in advanced HCC remains experimental with limited clinical data.

Eligibility criteria

Inclusion Criteria:

1. Aged 18 to 75 years (inclusive)
2. Histologically confirmed advanced hepatocellular carcinoma (HCC) with:

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1. Radiologically measurable disease per RECIST v1.1
2. 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:

1. White blood cell count (WBC) ≥3.0 × 10⁹/L
2. Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
3. Hemoglobin ≥9.0 g/dL (≥5.6 mmol/L)
4. 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:

1. Serum creatinine ≤1.5 × ULN OR
2. Calculated creatinine clearance (CrCl) ≥50 mL/min (Cockcroft-Gault formula) (4)Coagulation:

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1. 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:

   1. Women of childbearing potential (WOCBP): Negative serum pregnancy test within 7 days prior to treatment initiation AND agreement to use highly effective contraception during study participation and for ≥120 days after last study intervention
   2. Men: Agreement to use barrier contraception during study participation and for ≥120 days after last study intervention 8.Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

   Exclusion Criteria:

   1.History of other active malignancies within the past 5 years, except:
   1. Adequately treated basal cell or squamous cell skin cancer
   2. Carcinoma in situ of the cervix
   3. 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.

   5.Active bacterial, fungal, or mycobacterial infection requiring systemic therapy (including untreated latent tuberculosis) 6.Active viral infections meeting any of the following:
   1. Detectable HBV DNA (if HBsAg positive or HBcAb positive)
   2. Detectable HCV RNA
   3. HIV infection (serologically confirmed)
   4. Active syphilis infection (serologically confirmed) 7.Active autoimmune disease requiring systemic immunosuppressive therapy (\>10 mg prednisone equivalent daily) within the past 2 years, except:

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   1. Vitiligo
   2. Type 1 diabetes mellitus
   3. Hypothyroidism stable on hormone replacement
   4. 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:

   (1)New York Heart Association (NYHA) Class III or IV congestive heart failure (2)Unstable angina pectoris (3)Uncontrolled cardiac arrhythmia (4)Uncontrolled hypertension (≥160/100 mmHg despite medication) (5)Clinically significant pulmonary disease 10.History of substance abuse or psychiatric/social condition that would impair ability to provide informed consent or comply with study requirements 11.History of severe (Grade ≥3) hypersensitivity reactions to vaccine components or investigational products, or any condition deemed by the investigator to pose an unacceptable risk for immunotherapy 12.Any condition that, in the opinion of the Investigator, would compromise patient safety or interfere with study participation or interpretation of results

Where this trial is running

Hangzhou, Zhejiang

• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Tingbo Liang

Conditions Advanced Hepatocellular Carcinoma