DNAJB1-PRKACA Vaccine with Nivolumab and Ipilimumab for Fibrolamellar Hepatocellular Carcinoma
This study is testing a new approach for people with fibrolamellar hepatocellular carcinoma (FLC), a type of liver cancer, or other solid tumors that have a specific genetic change (DNAJB1-PRKACA fusion). It combines a vaccine called DNAJB1-PRKACA peptide vaccine with two other drugs, nivolumab and ipilimumab. These drugs are checkpoint inhibitors, which help your immune system fight cancer. The main goals are to see if this combination is safe and well-tolerated, and to measure the immune response (T-cell response) it creates. Researchers will also look at how long people live without their cancer growing (progression-free survival) in one group of participants. You may be able to join if you are over 12 years old and have FLC that has spread or cannot be removed by surgery, or certain other solid tumors with the DNAJB1-PRKACA fusion.
- Study design
- This is an interventional study with a planned enrollment of 56 participants. It is not specified if it is randomized or blinded.
- What's involved
- You would receive the DNAJB1-PRKACA peptide vaccine, nivolumab, and ipilimumab on specific schedules over several cycles. The study will measure your immune response at baseline and 10 weeks.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will measure drug-related toxicities for up to 4 years. Progression-free survival will be measured at 6 months for one group.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04248569
DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma
Recruiting
PHASE1Ages 12+InterventionalTreatmentSidney Kimmel Comprehensive Cancer Center at Johns HopkinsInvestigator-initiated
~56 participants
Updated 2025-12-03 on ClinicalTrials.gov
What's tested:DNAJB1-PRKACA peptide vaccineNivolumabIpilimumab
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
All Cohorts: Number of participants experiencing study drug-related toxicities
Measured over 4 years
+2 more outcomes measured
Conditions
NCT04248569
Where you'd take part
This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Marylandstudy coordinator listed
Recruiting
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Mark Yarchoan, MD · PRINCIPAL_INVESTIGATOR · Johns Hopkins Medical Institution
Who to contact
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Eligibility criteria
Inclusion
Cohort A and B: Must have histologically confirmed FLC (fibrolamellar hepatocellular cancer) that is metastatic or unresectable.
Cohort C: Patients with histologically proven metastatic or unresectable DNAJB1-PRKACA fusion transcript positive solid tumor malignancies, non-FLC solid tumors.
Cohort A and B: Age \> 12 years. Note: Subjects age \> 12 years but \<18 are eligible to enroll only after 6 adult patients have enrolled on the study.
Cohort A and B: Patients \< 18 years old must have a body weight ≥40 kg.
Cohort C: Patients must be Age ≥ 18 years.
Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing, DNA-sequencing, or in situ hybridization in the archival tissue.
ECOG performance status of ≤2 (Karnofsky ≥60%)
Patients must have adequate liver, kidney and marrow function defined by study-specified laboratory tests prior to initial study drug.
Patients must have measurable disease per RECIST 1.1.
Must be willing to provide tissue and blood samples for mandatory translational research.
Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
Men must use acceptable form of birth control while on study.
Ability to understand and willingness to sign a written informed consent document.
Patients previously treated with the vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with nivolumab and ipilimumab, who, in the opinion of the principal investigator, had clinical or radiological benefits.
Patients \< 18 years old must have a body weight ≥40 kg.
ECOG performance status of ≤2 (Karnofsky ≥60%, see Appendix A).
Patients must have adequate liver, kidney and marrow function defined by study-specified laboratory tests prior to initial study drug.
Patients must have measurable disease per RECIST 1.1.
Willingness to provide tissue and blood samples for mandatory translational research.
Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
Men must use acceptable form of birth control while on study.
Ability to understand and willingness to sign a written informed consent document.
Exclusion
Cohort A and C: Patients with a history of prior treatment with checkpoint inhibitors, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4, or anti-LAG-3 antibodies. NOTE: Prior therapy with interferon-alpha is allowed.
Cohort B: Participants a with history of unacceptable, life-threatening toxicity related to prior immune therapy (eg, anti-CTLA-4 or anti-PD-1/PD-L1 treatment, any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, hormone replacement after endocrinopathy).
Have had chemotherapy or other systemic therapy or radiotherapy, as follows:
Have had chemotherapy, biological cancer therapy, or radiation 14 days prior to the first dose of study drug.
Have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.
Have received other approved or investigational agents or device within 28 days of the first dose of study drug.
Have not recovered from acute adverse events to grade ≤1 or baseline due to agents administered.
Have received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment
Known sensitivity to or history of allergic reactions to investigational drug (s).
Hypersensitivity reaction to any monoclonal antibody.
Has 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 systemic steroids or immunosuppressive agents.
Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoeitic 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 of study drug administration.
Symptomatic interstitial lung disease.
Has a pulse oximetry of \<92% on room air or is on supplemental home oxygen.
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, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
Are pregnant or breastfeeding.
Infection with HIV or hepatitis B or C.
Have had evidence of active or acute diverticulitis, intra-abdominal abscess, or GI obstruction.
Unwilling or unable to follow the study schedule for any reason.
Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
Any illicit drugs or other substance abuse.
Clinically meaningful ascites.
Participants with a history of prior unacceptable and/or life-threatening toxicities.
Patients who have had chemotherapy or other systemic therapy or radiotherapy, as follows:
Patients who have had chemotherapy, biological cancer therapy, or radiation 14 days prior to the first dose of study drug.
Patients who have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.
Patients who have received other approved or investigational agents or device within 28 days of the first dose of study drug.
Patients who have not recovered from acute adverse events to grade ≤1 or baseline due to agents administered, with exception of alopecia or stable neuropathy, unless approved by the IND Sponsor.
Patients who have received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment.
Known sensitivity to or history of allergic reactions to investigational drug (s).
Hypersensitivity reaction to any monoclonal antibody.
Has 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 systemic steroids or immunosuppressive agents.
Has 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 systemic steroids or immunosuppressive agents.
Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoeitic 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 of study drug administration.
Symptomatic interstitial lung disease.
Has a pulse oximetry of \<92% on room air or is on supplemental home oxygen.
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, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
Are pregnant or breastfeeding.
Infection with HIV or hepatitis B or C.
Have had evidence of active or acute diverticulitis, intra-abdominal abscess, or GI obstruction.
Unwilling or unable to follow the study schedule for any reason.
Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
Any illicit drugs or other substance abuse.
Clinically meaningful ascites.
What this trial measures
- All Cohorts: Number of participants experiencing study drug-related toxicities4 years
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
- All Cohorts: Fold change in interferon-producing DNAJB1-PRKACA-specific CD4 and CD8 T cells at 10 weeksBaseline and 10 weeks
Evaluated by the fold change in interferon-producing DNAJB1-PRKACA-specific CD8 cells after vaccination at 10 weeks compare to pre-vaccination baseline.
- Cohort A only: Progression-free survival (PFS)6 months
PFS at 6 months, will be estimated as the proportion of subjects who remain alive and free of disease progression at 6 months from the start of treatment. Disease progression will be determined using RECIST 1.1 criteria. The proportion of subjects achieving PFS at 6 months will be estimated using the Kaplan-Meier method, and the corresponding 95% confidence interval will be reported.