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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 1INTERVENTIONAL

DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma

A Pilot Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma

DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma (NCT04248569) is a Phase 1 interventional studying Fibrolamellar Hepatocellular Carcinoma (FLC), sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The primary objective of the trial is the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in patients with unresectable or metastatic FLC and with non-FLC solid tumors and to assess the T-cell response.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Fibrolamellar Hepatocellular Carcinoma (FLC), a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 56 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Fibrolamellar Hepatocellular Carcinoma (FLC) subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Inclusion Criteria for Cohort A, B and C: - Cohort A and B: Must have diagnosed by tissue sample (biopsy-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. All Cohorts: - 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 tumors that can be measured on scans 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 willing to sign a consent form document. Exclusion Criteria for Cohorts A, B and C: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria for Cohort A, B and C: * 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. All Cohorts: * 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. Exclusion Criteria for Cohorts A, B and C: * 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). All Cohorts: * 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. Inclusion Criteria for Re-Enrolling Patients: * 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 Criteria for Re-Enrolling Patients: * 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.

Treatments Being Tested

DRUG

DNAJB1-PRKACA peptide vaccine

1. DNAJB1-PRKACA peptide vaccine: Day 1, 8, 15 of cycle 1 and on Day 1 of cycle 2, 3 and 4 (priming phase). Boost vaccinations: every 3 cycles beginning C5D1. 2. Drug: 0.3 mg DNAJB1-PRKACA peptide vaccine + 0.5mg Poly-ICLC

DRUG

Nivolumab

1. Nivolumab 3mg/kg will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycle 1-4 during the priming phase. Boost/maintenance vaccinations will be administered as a flat dose of 480mg every 4 weeks starting on Day 1 of Cycle 5. 2. Drug: 3mg/kg and 480mg IV

DRUG

Ipilimumab

1. Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycles 1, 2, 3 and 4 of the study, every 3 weeks of the priming phase. 2. Drug: 1mg/kg IV

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04248569), the sponsor (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04248569 clinical trial studying?

The primary objective of the trial is the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in patients with unresectable or metastatic FLC and with non-FLC solid tumors and to assess the T-cell response. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04248569?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04248569?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04248569. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04248569. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.