Fibrolamellar Hepatocellular CarcinomaPhase 1FusionVAC22NCT05937295
FusionVAC22_01: Fusion Transcript-based Peptide Vaccine Combined with Immune Checkpoint Inhibition
A Phase 1 study testing Fusion-VAC-XS15 in people with Fibrolamellar Hepatocellular Carcinoma, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fibrolamellar Hepatocellular Carcinoma
- What is being tested?
- Fusion-VAC-XS15
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 26 Sep 2023to Jan 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- Pregnant or breastfeeding.
- Unwilling or unable to follow the study schedule for any reason.
- Chemotherapy or other systemic therapy or radiotherapy, up to 14 days prior to the first dose of study drug.
- Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anticancer therapy or any other investigational therapy, which would interfere with the study's primary and secondary endpoints.
- Major surgery within 28 days of dosing of study drug.
- Have not recovered from adverse events to grade ≤ 2 or baseline due to previous agents administered excluding alopecia and neurotoxicity (≤ 2 grade).
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- History of autoimmune phenomena due to treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibodies, etc.) (≥ grade 3).
- Treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibodies, etc.) within 28 days prior of dosing of study drug.
- Have received any live vaccine within 28 days prior to study treatment.
- Known sensitivity to or history of allergic reactions to any of the investigational drugs or known hypersensitivity to Chinese hamster ovary cell products.
- History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins.
- Has active autoimmune disease that requires or has required systemic immunosuppressive treatment in the past 2 years.
- Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.
- Has a diagnosis of immunodeficiency.
- Systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days prior to study drug administration.
- Symptomatic interstitial lung disease.
- Active or untreated brain metastases or leptomeningeal metastases.
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, different metastatic cancer than the one leading to study enrollment, or psychiatric illness/social
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Tuebingen
Tübingen, Baden-Würtemberg, 72076
Juliane Walz, Prof. Dr., +49 (0)707129 ext. 83275, kketi@med.uni-tuebingen.de
Hackenbruch, +49 (0)707129 ext. 83275
About this study
Official title: 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.
- Conditions
- Fibrolamellar Hepatocellular Carcinoma
- Being tested
- Fusion-VAC-XS15
- Keywords
- FL_HCC, DNAJB1-PRKACA
- Medical subject headings
- Fibrolamellar hepatocellular carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fusion-VAC-XS15Drug
FusionVAC-22 peptide will be administered subcutaneously (s.c.) adjuvanted with the Toll-like receptor 1/2 ligand XS15 (50 μg) emulsified in Montanide ISA 51 VG (1:1).
Vaccination will take place every 4 weeks at the beginning of Cycle 1 and 2. A total of two vaccinations are planned.
After 11 months a booster vaccination can be applied depending on T-cell responses.
Immune checkpoint inhibition (ICI):
Atezolizumab (TecentriqTM, Roche Pharma AG) is a humanized immunoglobulin (Ig) G1 monoclonal antibody that targets PD-L1 and will be applied intravenously (i.v.).
The anti-PD-L1 antibody Atezolizumab (TecentriqTM) 1680 mg will be applied every 4 weeks as a 30-minute infusion (60-minute first dose) starting on day 15 after the first vaccination. Anti-PD-L1 treatment will be continued after the end of vaccination phase throughout the complete study period until End of Treatment (EOT) or until disease progression or other reasons for study termination.
| Study group | Role | What they receive |
|---|---|---|
| FusionVAC-XS15 and Atecolizumab treatment | Experimental | Not described Receives: Drug: Fusion-VAC-XS15 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess immunogenicity in terms of induction of peptide specific T-cell responses
The percentage of patients with an induction of T-cell response until 28 days after second vaccination will be the primary endpoint for efficacy. Peptide stimulated Peripheral Blood Mononuclear Cells (PBMCs) are analyzed by enzyme-linked immunospot (ELISPOT).
Measured: through study completion, an average of 1 year
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of the peptide vaccine in combination with anti-PD-L1 immune checkpoint inhibition
The safety and toxicity of the personalized multi-peptide vaccine in combination with the toll-like receptor1/2 ligand XS15 with anti-PD-L1 immune checkpoint inhibition (ICI) will be determined based on the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and assessed in a descriptive manner.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2023
- Study start26 Sep 2023
- Primary completionSep 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fibrolamellar Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase I, open-label, multicenter, interventional clinical trial
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Salih, Prof. Dr., Principal investigator, CCU Translational Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05937295
- Sponsor's protocol ID
- FusionVAC22_01
- Other IDs
- 2022-502869-17-01
- Acronym
- FusionVAC22
- Status last verified
- Nov 2024
- First submitted
- 9 May 2023
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hackenbruch C, Bauer J, Heitmann JS, Maringer Y, Nelde A, Denk M, Zieschang L, Kammer C, Federmann B, Jung S, Martus P, Malek NP, Nikolaou K, Salih HR, Bitzer M, Walz JS. 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. Front Oncol. 2024 Mar 28;14:1367450. doi: 10.3389/fonc.2024.1367450. eCollection 2024.
PubMed 38606105
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05937295
- Acronym / sponsor ID
- FusionVAC22 / FusionVAC22_01
- Conditions
- Fibrolamellar Hepatocellular Carcinoma
- Keywords
- FL_HCC, DNAJB1-PRKACA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 26 Sep 2023 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 10 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase I, open-label, multicenter, interventional clinical trial
| Arm | Type | Receives |
|---|---|---|
| FusionVAC-XS15 and Atecolizumab treatment | Experimental | Drug: Fusion-VAC-XS15 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
- 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.
Key exclusion criteria (18 listed)
- Pregnant or breastfeeding.
- Unwilling or unable to follow the study schedule for any reason.
- Chemotherapy or other systemic therapy or radiotherapy, up to 14 days prior to the first dose of study drug.
- Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anticancer therapy or any other investigational therapy, which would interfere with the study's primary and secondary endpoints.
- Major surgery within 28 days of dosing of study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fusion-VAC-XS15FusionVAC-22 peptide will be administered subcutaneously (s.c.) adjuvanted with the Toll-like receptor 1/2 ligand XS15 (50 μg) emulsified in Montanide ISA 51 VG (1:1). Vaccination will take place every 4 weeks at the beginning of Cycle 1 and 2. A total of two vaccinations are planned. After 11 months a booster vaccination can be applied depending on T-cell responses. Immune checkpoint inhibition (ICI): Atezolizumab (TecentriqTM, Roche Pharma AG) is a humanized immunoglobulin (Ig) G1 monoclonal antibody that targets PD-L1 and will be applied intravenously (i.v.). The anti-PD-L1 antibody Atezolizumab (TecentriqTM) 1680 mg will be applied every 4 weeks as a 30-minute infusion (60-minute first dose) starting on day 15 after the first vaccination. Anti-PD-L1 treatment will be continued after the end of vaccination phase throughout the complete study period until End of Treatment (EOT) or until disease progression or other reasons for study termination. | Drug | FusionVAC-XS15 and Atecolizumab treatment |
Primary outcome
To assess immunogenicity in terms of induction of peptide specific T-cell responses
Time frame: through study completion, an average of 1 year
The percentage of patients with an induction of T-cell response until 28 days after second vaccination will be the primary endpoint for efficacy. Peptide stimulated Peripheral Blood Mononuclear Cells (PBMCs) are analyzed by enzyme-linked immunospot (ELISPOT).
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of the peptide vaccine in combination with anti-PD-L1 immune checkpoint inhibition
Time frame: through study completion, an average of 1 year
The safety and toxicity of the personalized multi-peptide vaccine in combination with the toll-like receptor1/2 ligand XS15 with anti-PD-L1 immune checkpoint inhibition (ICI) will be determined based on the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and assessed in a descriptive manner.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
- Derived from this study: PubMed 38606105Hackenbruch C, Bauer J, Heitmann JS, Maringer Y, Nelde A, Denk M, Zieschang L, Kammer C, Federmann B, Jung S, Martus P, Malek NP, Nikolaou K, Salih HR, Bitzer M, Walz JS. 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. Front Oncol. 2024 Mar 28;14:1367450. doi: 10.3389/fonc.2024.1367450. eCollection 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Salih, Prof. Dr. principal investigator
CCU Translational Immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fusion-VAC-XS15 in people with Fibrolamellar Hepatocellular Carcinoma, run by University Hospital Tuebingen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Juliane Walz, Prof. Dr. (+49(0)707129 ext. 83275, kketi@med.uni-tuebingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess immunogenicity in terms of induction of peptide specific T-cell responses (time frame: through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05937295, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.