Fusion-VAC-XS15 / University Hospital Tuebingen - LARVOL DELTA

FusionVAC22_01, phase I clinical Trial in Progress: DNAJB1::PRKACA fusion transcript-based peptide T cell activator combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion in advanced or metastatic situation (DGHO 2025) - P1 | "Commun., 2022).FusionVAC22_01 is a Phase I open label, multicentric clinical trial evaluating immunogenicity along with safety, toxicity and first signs of efficacy of the T cell activator Fusion-VAC-XS15 combined with the immune checkpoint inhibitor (ICI) Atezolizumab, in 20 patients with locally advanced or metastatic FL-HCC or other cancers with proven DNAJB1::PRKACA fusion transcript (Hackenbruch et al. The first patient has completed the 12 months end of study with continuing benefit, enabling resection of remaining tumor lesions. Clinical trial information: NCT05937295.Fusion-VAC-XS15 combined with ICI is an innovative and promising immunotherapeutic approach for the devastating tumor FL-HCC and other cancers carrying the DNAJB1::PRKACA fusion transcript."

Checkpoint inhibition • Clinical • Metastases • P1 data • Hepatocellular Cancer • Oncology • Pancreatic Cancer • Solid Tumor • DNAJB1 • PRKACA

FusionVAC22_02, a phase I clinical Trial in Progress: DNAJB1::PRKACA fusion transcript-based peptide T cell activator for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion in the adjuvant situation (DGHO 2025) - P1 | "Commun., 2022).Based on these promising data Fusion-VAC-XS15 combined with Atezolizumab is currently under evaluation in the advanced or metastatic situation since October 2023 (Hackenbruch et al. Recruitment will start in May 2025. Clinical trial information: NCT06789198.Fusion-VAC-XS15 is an innovative and promising immunotherapeutic treatment option in the adjuvant setting for FL-HCC and other cancers carrying the DNAJB1::PRKACA fusion transcript."

Clinical • P1 data • Hepatocellular Cancer • Oncology • Pancreatic Cancer • Solid Tumor • DNAJB1 • PRKACA

FusionVAC22_02: Peptide Vaccine for Fibrolamellar Hepatocellular Carcinoma Patients and Other Tumor Entities Carrying the Driver Fusion DNAJB1-PRKACA (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: University Hospital Tuebingen

New P1 trial • Hepatocellular Cancer • Oncology • Solid Tumor • IFNG

FusionVAC22_01: Phase I study to evaluate treatment with a DNAJB1-PRKACA fusion transcript peptide vaccine and immune checkpoint inhibition in patients with fibrolamellar hepatocellular carcinoma and other tumor entities that harbor the oncogenic driver fusion – Trial in Progress (DGHO 2024) - P1 | "Based on these promising data, we started a Phase I open label, multicentric clinical trial evaluating immunogenicity along with safety, toxicity and first signs of efficacy of Fusion-VAC-XS15 (FusionVAC-22-based peptide vaccine) combined with the immune checkpoint inhibitor (ICI) Atezolizumab, in 20 patients with locally advanced or metastatic FL-HCC or other cancer with proven DNAJB1-PRKACA fusion transcript without available standard therapy (Hackenbruch et al. Also, disease control rate, quality of life, and overall-/ progression-free survival will be evaluated. So far, 4 patients have been vaccinated."

Checkpoint inhibition • Clinical • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Immunology • Oncology • Pancreatic Cancer • Solid Tumor • DNAJB1 • PRKACA

iVAC-XS15-CLL01: Personalized multi-peptide vaccination in combination with the TLR1/2 ligand XS15 in CLL patients undergoing BTK-inhibitor-based regimens (Frontiers) - "The iVAC-XS15-CLL01 trial is an open-label, first-in-human (FIH) Phase I trial, evaluating the CLL-VAC-XS15 vaccine in CLL patients undergoing BTKi-based therapy...To facilitate rapid and cost-effective deployment, vaccine peptides are selected for each patient from a premanufactured 'peptide warehouse' based on the patient's individual HLA allotype and CLL immunopeptidome. The trial enrolls 20 CLL patients, who receive up to three doses of the vaccine, adjuvanted with the toll-like-receptor (TLR) 1/2 ligand XS15 and emulsified in Montanide ISA 51 VG. The primary objective of the iVAC-XS15-CLL01 trial is to assess the safety and immunogenicity of the CLL-VAC-XS15 vaccine."

Clinical protocol • Chronic Lymphocytic Leukemia

FusionVAC22_01: A phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion. (ASCO 2024) - P1 | " Building on these promising outcomes, we have initiated a Phase I open-label, multicentric clinical trial to assess the immunogenicity, safety, toxicity, and initial signs of efficacy of the FusionVAC-22-based peptide vaccine combined with the immune checkpoint inhibitor (ICI) atezolizumab. Bauer et al., Nat. Commun, 2022."

Checkpoint inhibition • Clinical • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Immunology • Oncology • Pancreatic Cancer • Solid Tumor • DNAJB1 • PRKACA

FusionVAC22_01: a phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion. (PubMed, Front Oncol) - P1 | "Two doses of the DNAJB1-PRKACA fusion-based neoepitope vaccine Fusion-VAC-XS15 will be applied subcutaneously (s.c.) with a 4-week interval in combination with the anti-programmed cell death-ligand 1 (PD-L1) antibody atezolizumab starting at day 15 after the first vaccination. Clinical trial results will be published in peer-reviewed journals. EU CT Number: 2022-502869-17-01 and ClinicalTrials.gov Registry (NCT05937295)."

Checkpoint inhibition • Journal • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • DNAJB1 • PRKACA

FusionVAC22_01: A phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion. (ASCO-GI 2024) - P1 | " Based on these encouraging results, we established a Phase I open-label, multicentric clinical trial to evaluate the immunogenicity along with safety and toxicity, as well as first signs of efficacy of the FusionVAC-22 based peptide vaccine, combined with the immune checkpoint inhibitor (ICI) atezolizumab, in 20 patients with locally advanced or metastatic FL-HCC or other malignant diseases that carry the DNAJB1-PRKACA fusion transcript. Furthermore, disease control rate, quality of life as well as overall and progression free survival will be assessed. Clinical trial information: NCT05937295."

Checkpoint inhibition • Clinical • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Pancreatic Cancer • Solid Tumor • DNAJB1 • PRKACA

FusionVAC22_01: Fusion Transcript-based Peptide Vaccine Combined With Immune Checkpoint Inhibition (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: University Hospital Tuebingen | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • DNAJB1 • PRKACA

FusionVAC22_01: A phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion (DGHO 2023) - "Most importantly, until now the second patient showed stable disease for 8 months after vaccination. Based on these promising data, we established a Phase I open label, multicentric clinical trial (EU-CT Number 2022-502869-17-00) evaluating the immunogenicity along with safety and toxicity, as well as first signs of efficacy of the FusionVAC-22 based peptide vaccine, combined with an ICI (anti-PD-L1), in 20 patients with locally advanced or metastatic FL-HCC or other malignant disease with proven presence of the DNAJB1-PRKACA fusion transcript."

Checkpoint inhibition • Clinical • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Pancreatic Cancer • Solid Tumor • DNAJB1 • PRKACA

FCF funds planned clinical trial at Johns Hopkins (Fibrolamellar Cancer Foundation) - "We are pleased to announce that FCF has awarded Dr. Marina Baretti and Dr. Mark Yarchoan...a grant to launch a new clinical trial for FLC patients. Both investigators have extensive experience in treating patients with FLC and in the development of immunotherapies. They already have collaborated closely on the clinical testing of a peptide vaccine targeting the DNAJB1-PRKACA fusion protein that drives the disease."

Announcement