Peptide vaccine targeting the DNAJB1-PRKACA fusion in fibrolamellar liver cancer and related tumors

FusionVAC22_02: DNAJB1-PRKACA Fusion Transcript-based Peptide Vaccine for Fibrolamellar Hepatocellular Carcinoma Patients and Other Tumor Entities Carrying the Oncogenic Driver Fusion

This trial tests whether a peptide vaccine called Fusion‑VAC‑XS15 can boost the immune system to prevent recurrence in people with fibrolamellar hepatocellular carcinoma or other tumors that carry the DNAJB1‑PRKACA fusion after they have reached complete remission.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: University Hospital Tuebingen (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 2 sites (Tübingen and 1 other locations)
• Trial ID: NCT06789198 on ClinicalTrials.gov

What this trial studies

This Phase 1 trial gives a peptide vaccine (FusionVAC-22 peptides formulated with the TLR1/2 ligand XS15 and Montanide ISA 51) to patients whose tumors carry the DNAJB1-PRKACA fusion in an adjuvant setting after complete remission. Two subcutaneous vaccinations are planned four weeks apart, with an optional booster about eight weeks after the second dose if a sufficient T-cell response is not observed. The primary goals are to test immunogenicity and safety/tolerability and to collect initial signals of anti-relapse efficacy. Eligible participants must have fusion confirmation by RNA-based NGS or RT-PCR, be age ≥12, have ECOG ≤2, and meet specified laboratory criteria, and all study visits occur at the University Hospital Tübingen.

Who should consider this trial

Good fit: Ideal candidates are people aged 12 and older with histologically confirmed fibrolamellar hepatocellular carcinoma or other cancers carrying the DNAJB1-PRKACA fusion who are in complete remission after surgery, radiotherapy, local or systemic therapy and who meet ECOG and laboratory requirements.

Not a fit: Patients with active measurable disease, tumors lacking the DNAJB1-PRKACA fusion, significant immunosuppression, or inadequate blood counts or organ function are unlikely to benefit from this vaccine approach.

Why it matters

Potential benefit: If successful, the vaccine could reduce relapse risk and prolong disease-free survival by helping the immune system eliminate residual fusion-positive tumor cells.

How similar studies have performed: Peptide vaccines and TLR-adjuvanted vaccines have produced immune responses in other cancers, but vaccines specifically targeting the DNAJB1-PRKACA fusion in FLC are novel and currently unproven.

Eligibility criteria

Inclusion Criteria:

* Ability to understand and willingness to sign a written informed consent document.
* Histologically confirmed Fibrolamellar hepatocellular carcinoma (FL-HCC) or other malignant disease in an adjuvant setting, defined as:

  * Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-based NGS or RT-PCR
  * Achievement of complete remission (CR) according to RECIST1.1 by any of the following therapeutic measures:
* surgical procedures,
* radiotherapy,
* local therapeutic measures (e.g. TACE, SIRT, etc.)
* systemic treatment (e.g. chemotherapy)
* Age ≥ 12 years. Note: Subjects aged ≥ 12 years but \< 18 are eligible to enroll only after 6 adult patients have been enrolled in the study.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Adequate laboratory values for

  * Absolute Lymphocyte Count \> 500 /µl
  * Platelets \> 50.000 /µl
  * Creatinine clearance GFR \> 30 ml/min
  * Alanine aminotransferase (ALT) and aminotransferase (AST) ≤ 5 times upper limit range
  * Bilirubin ≤ 3 mg/dl
* Negative serological hepatitis B test or negative PCR in case of positive serological test without evidence of an active infection, negative testing of hepatitis C RNA, negative HIV test within 6 weeks prior to study inclusion.
* Female patients of child bearing potential (FCBP) and male patients with partners of child bearing potential who are sexually active must agree to the use of two effective forms (at least one highly effective method) of contraception. This should be started from the signing of the informed consent and be continued until 3 months (both female and male patients) after last dose of the vaccination
* For FCBP two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to first application of the study drug (vaccination at visit V1), one at screening and the other one at visit V1 prior (\< 24h) to first vaccination.
* Postmenopausal or evidence of non-child-bearing status.
* Be willing to minimize blood and body fluid exposure after vaccination until end of study

  * Refrain from sperm or ovary egg donation
  * Refrain from blood donation

Exclusion Criteria:

* Pregnant or breastfeeding.
* Unwilling or unable to follow the study schedule for any reason.
* Concurrent or previous treatment within 14 days in another interventional clinical trial with an investigational anti-cancer treatment.
* Concurrent treatment with any of the following therapeutic measures:

  * surgical procedures,
  * radiotherapy,
  * local therapeutic measures (e.g. TACE, SIRT, etc.)
  * systemic treatment (e.g. chemotherapy)
* Concurrent or previous treatment within 6 months with an anti-cancer vaccine treatment.
* Any live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment
* Known sensitivity to or history of allergic reactions to investigational drug.
* Active autoimmune disease that has required systemic treatment in the past 2 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids (\> 10 mg per day) or immunosuppressive agents (Please note, patients after liver transplantation requiring immunosupressants are allowed).
* Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.

Where this trial is running

Tübingen and 1 other locations

• University Hospital Tuebingen — Tübingen, Germany (Recruiting)
• Universitätsklinikum Tübingen, Kinderheilkunde I — Tübingen, Germany (Not_yet_recruiting)

Study contacts

• Study coordinator: Juliane Walz, Prof. Dr.

Conditions Fibrolamellar Hepatocellular Carcinoma; DNAJB1-PRKACA fusion transcript; Fibrolamellar hepatocellular carcinoma