FusionVAC22_02: DNAJB1-PRKACA fusion transcript-based peptide vaccine for fibrolamellar hepatocellular carcinoma patients and other tumor entities carrying the oncogenic driver fusion

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

7 May 2025 → ongoing

Decision date (initial)

2025-03-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Fibriolammelar Cancer Foundation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Therapy, Pharmacokinetic

The aim of this clinical trial is to evaluate the immunogenicity along with safety and toxicity as well as first efficacy of a DNAJB1-PRKACA fusion transcript-based peptide vaccine (Fusion-VAC-XS15) in patients with FL-HCC or other cancer entities carrying the DNAJB1-PRKACA fusion transcript as adjuvant treatment

Conditions and MedDRA coding

tumor entities carrying the oncogenic driver fusion

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Ability to understand and willingness to sign a written informed consent document.
2. Be willing to minimize blood and body fluid exposure after vaccination until end of studyo Refrain from sperm or ovary egg donationo Refrain from blood donation
3. Histologically confirmed FL-HCC or other malignant disease in an adjuvant setting defined as:o Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-based NGS or RT-PCRo 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)
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. 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
7. Negative serological hepatitis B test or negative PCR in case of positive serological test without evidence of an active infection, negative serological testing of hepatitis C or negative PCR, negative HIV test within 6 weeks prior to study inclusion
8. 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
9. 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
10. Postmenopausal or evidence of non-child-bearing status
11. For other malignant disease: no established (per local regulations) adjuvant treatment is available or patients are ineligible to receive it

Exclusion criteria 9

1. Pregnant or breastfeeding.
2. Unwilling or unable to follow the study schedule for any reason
3. Concurrent or previous treatment within 14 days in another interventional clinical trial with an investigational anti-cancer treatment
4. Planned intitiation of treatment with any of the following therapeutic measures: o surgical procedures, o radiotherapy, o local therapeutic measures (e.g. TACE, SIRT, etc.) o systemic treatment (e.g. chemotherapy) o Of note: ongoing systemic treatment (e.g. maintenance) is allowed per investigator’s discretion
5. Concurrent or previous treatment within 6 months with an anti-cancer vaccine treatment
6. Any live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment
7. Known sensitivity to or history of allergic reactions to investigational drug
8. 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 ongoing systemic steroids (> 10 mg per day) or immunosuppressive agents (please note, patients after liver transplantation requiring immunosupressants are allowed).
9. Uncontrolled intercurrent illness including: active autoimmune disease as stated above, uncontrolled infection, symptomatic congestive heart failure, unstable angina, severe obstructive or restrictive ventilation disorder, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The study analyses efficacy and safety as primary objectives. Primary objectives of the planned trial are (i) to assess immunogenicity in terms of induction of peptide specific T-cell responses and (ii) to assess safety and toxicity of the peptide vaccine. The safety and toxicity of the DNAJB1-PRKACA fusion transcript-based peptide vaccine is determined based on the Common Terminology Criteria for Adverse Events (CTCAE V 5.0) and assessed in a descriptive manner

Secondary endpoints 7

1. Percentage of patients with induction of a peptide specific T-cell response at eachscheduled visit until EOS visit compared to baseline (visit V1 prior to first vaccination)as determined by IFNγ ELISPOT
2. Number and percentage of patients receiving a booster vaccination or to be scheduledto receive a booster vaccination out of all patients
3. Incidence and severity of adverse events (AEs) including AESIs, SAEs and SUSARs(CTCAE V5.0) from first vaccination at visit V1 until end of study (EOS) visit or, incase of early termination before EOT or EOT (B), last assessment.
4. Disease control rate (CR, PR, SD) ) assessed by RECIST1.1 at each visit until end of study
5. PFS from the date of first vaccination until the date of progressive disease accordingto RECIST1.1 or death from any cause
6. OS from the date of first vaccination until the date of death from any cause
7. Overall quality of life scores (EORTC QLQ C-30) at every scheduled visit until EOSvisit.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

CCU Translational Immunology

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

CCU Translational Immunology

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications