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FusionVAC22_01: Fusion Transcript-based Peptide Vaccine Combined With Immune Checkpoint Inhibition (FusionVAC22)

Primary Purpose

Fibrolamellar Hepatocellular Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Fusion-VAC-XS15
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fibrolamellar Hepatocellular Carcinoma focused on measuring FL_HCC, DNAJB1-PRKACA

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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). 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

Sites / Locations

  • University Hospital TuebingenRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FusionVAC-XS15 and Atecolizumab treatment

Arm Description

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

Full Information

First Posted
May 9, 2023
Last Updated
September 27, 2023
Sponsor
University Hospital Tuebingen
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1. Study Identification

Unique Protocol Identification Number
NCT05937295
Brief Title
FusionVAC22_01: Fusion Transcript-based Peptide Vaccine Combined With Immune Checkpoint Inhibition
Acronym
FusionVAC22
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 26, 2023 (Actual)
Primary Completion Date
September 2026 (Anticipated)
Study Completion Date
January 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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) in patients with Fibrolamellar hepatocellular carcinoma (FL-HCC) or other cancer entities carrying the DNAJB1-PRKACA fusion transcript.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibrolamellar Hepatocellular Carcinoma
Keywords
FL_HCC, DNAJB1-PRKACA

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Phase I, open-label, multicenter, interventional clinical trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FusionVAC-XS15 and Atecolizumab treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Fusion-VAC-XS15
Intervention Description
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.
Primary Outcome Measure Information:
Title
To assess immunogenicity in terms of induction of peptide specific T-cell responses
Description
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).
Time Frame
through study completion, an average of 1 year
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of the peptide vaccine in combination with anti-PD-L1 immune checkpoint inhibition
Description
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.
Time Frame
through study completion, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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). 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Juliane Walz, Prof. Dr.
Phone
+49(0)707129
Ext
83275
Email
kketi@med.uni-tuebingen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Salih, Prof. Dr.
Organizational Affiliation
CCU Translational Immunology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Tuebingen
City
Tuebingen
State/Province
Baden-Würtemberg
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juliane Walz, Prof. Dr.
Phone
+49 (0)707129
Ext
83275
Email
kketi@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Hackenbruch
Phone
+49 (0)707129
Ext
83275
First Name & Middle Initial & Last Name & Degree
Salih, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Heitmann, Dr.
First Name & Middle Initial & Last Name & Degree
Bitzer, Prof. Dr.

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

FusionVAC22_01: Fusion Transcript-based Peptide Vaccine Combined With Immune Checkpoint Inhibition

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