FusionVAC22_01: 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
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 combination with anti-programmed cell death-ligand 1 immune checkpoint inhibition (ICI) by Atezolizumab (TecentriqTM) in patients with Fibrolamellar hepatocellular carcinoma (FL-HCC) or other cancer entities carrying the DNAJB1-PRKACA fusion transcript.
• Ability to understand and willingness to sign a written informed consent document.
• Histologically confirmed FL-HCC or other malignant disease that is locally advanced or metastatic.
• Non-FL-HCC patients can be included
‣ in case of disease progression after therapy and fulfilling at least one of the following criteria: i. no further standard therapy is available. ii. patient is considered unsuitable for further available standard therapy. iii. patient is unwilling to receive treatment with available standard therapy.
⁃ if no standard therapy exists.
• Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-based next-generation sequencing (NGS) or realtime-polymerase chain reaction amplification (RT-PCR).
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients must have measurable disease per iRECIST (Response Evaluation Criteria in Solid Tumours).
• Negative SARS-CoV-2 rapid antigen test (as long as World Health Organization declares pandemic spread of SARS-CoV-2).
• Adequate organ function laboratory values
∙ Absolute Lymphocyte Count \> 500/μl
‣ Platelets \> 50.000/μl
‣ Creatinine clearance glomerular filtration rate \> 30 ml/min
‣ Liver function Child-Pugh index class A or B7
‣ 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 5 months (both female and male patients) after last dose of an Atezolizumab (TecentriqTM) or vaccination.
• For FCBP two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to first application of a 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.