DNAJB1-PRKACA TRIFLUORACETATE for Fibrolamellar hepatocellular carcinoma|Tumors carrying DNAJB1-PRKACA fusion

Inclusion criteria

• {"criterion_text":"- Ability to understand and willingness to sign a written informed consent document.\n- Postmenopausal or evidence of non-child-bearing status\n- For other malignant disease: no established (per local regulations) adjuvant treatment is available or patients are ineligible to receive it\n- Be willing to minimize blood and body fluid exposure after vaccination until end of studyo\tRefrain from sperm or ovary egg donationo\tRefrain from blood donation\n- Histologically confirmed FL-HCC or other malignant disease in an adjuvant setting defined as:o\tPresence of DNAJB1-PRKACA fusion transcript, assessed by RNA-based NGS or RT-PCRo\tAchievement of complete remission (CR) according to RECIST1.1 by any of the following therapeutic measures:•\tsurgical procedures, •radiotherapy, •local therapeutic measures (e.g. TACE, SIRT, etc.) •systemic treatment (e.g. chemotherapy)\n- 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.\n- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.\n- Adequate laboratory values for-\tAbsolute Lymphocyte Count > 500 /µl-\tPlatelets > 50.000 /µl \tCreatinine clearance GFR > 30 ml/min Alanine aminotransferase (ALT) and aminotransferase (AST) ≤ 5 times upper limit range\t Bilirubin ≤ 3 mg/dl\n- 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\n- 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\n- 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"}

Exclusion criteria

• {"criterion_text":"- Pregnant or breastfeeding.\n- Unwilling or unable to follow the study schedule for any reason\n- Concurrent or previous treatment within 14 days in another interventional clinical trial with an investigational anti-cancer treatment\n- Planned intitiation of treatment with any of the following therapeutic measures: o\tsurgical procedures, o\tradiotherapy, o\tlocal therapeutic measures (e.g. TACE, SIRT, etc.) o\tsystemic treatment (e.g. chemotherapy) o\tOf note: ongoing systemic treatment (e.g. maintenance) is allowed per investigator’s discretion\n- Concurrent or previous treatment within 6 months with an anti-cancer vaccine treatment\n- Any live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment\n- Known sensitivity to or history of allergic reactions to investigational drug\n- 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).\n- 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"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Immunogenicity: induction of peptide-specific T-cell responses (measured as peptide specific T-cell responses). Safety/toxicity: determined based on Common Terminology Criteria for Adverse Events (CTCAE V5.0) and assessed descriptively."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured by IFNγ ELISPOT comparing each scheduled visit to baseline (visit V1 prior to first vaccination)."}
• {"endpoint_text":"- Number and percentage of patients receiving a booster vaccination or to be scheduledto receive a booster vaccination out of all patients","definition_or_measurement_approach":"Count and percentage of patients receiving or scheduled to receive a booster vaccination."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"AEs, AESIs, SAEs, SUSARs graded per CTCAE V5.0 from first vaccination until EOS or last assessment."}
• {"endpoint_text":"- Disease control rate (CR, PR, SD) ) assessed by RECIST1.1 at each visit until end of study","definition_or_measurement_approach":"Disease control rate assessed by RECIST 1.1 (CR, PR, SD) at each visit until end of study."}
• {"endpoint_text":"- PFS from the date of first vaccination until the date of progressive disease accordingto RECIST1.1 or death from any cause","definition_or_measurement_approach":"Progression-free survival measured from first vaccination to progression per RECIST1.1 or death from any cause."}
• {"endpoint_text":"- OS from the date of first vaccination until the date of death from any cause","definition_or_measurement_approach":"Overall survival measured from first vaccination to death from any cause."}
• {"endpoint_text":"- Overall quality of life scores (EORTC QLQ C-30) at every scheduled visit until EOSvisit.","definition_or_measurement_approach":"Quality of life assessed using EORTC QLQ-C30 at each scheduled visit until EOS."}

Germany

Earliest CTIS Part Ii Submission Date

19-02-2025

Latest Decision Or Authorization Date

20-03-2025

Processing Time Days

29

Number Of Sites

2

Number Of Participants

20

Primary sponsor

Full Name

Universitaetsklinikum Tuebingen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany