Fibrolamellar Hepatocellular Carcinoma (FLC)Phase 1NCT04248569
DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma
A Phase 1 study testing DNAJB1-PRKACA peptide vaccine, Nivolumab and Ipilimumab in people with Fibrolamellar Hepatocellular Carcinoma (FLC), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Fibrolamellar Hepatocellular Carcinoma (FLC)
- What is being tested?
- DNAJB1-PRKACA peptide vaccine, Nivolumab and Ipilimumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Apr 2020to 1 Mar 2034
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
Show all 23Show fewer
- 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.
Who cannot join
- 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.
Show all 51Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
Colleen Apostol, RN, 410-614-3644, GIClinicalTrials@jhmi.edu
Marina Baretti, MD, 410-614-1058, mbarett1@jhu.edu
About this study
Official title: A Pilot Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma
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.
- Being tested
- DNAJB1-PRKACA peptide vaccine, Nivolumab, Ipilimumab
- Keywords
- DNAJB1-PRKACA Peptide Vaccine, Nivolumab, Ipilimumab, Anti-PD-1 (receptor blocking antibody), Anti-CTLA-4 (receptor blocking antibody), Neoantigen Vaccines, Cancer Vaccines, Immunotherapy, Fibrolamellar Hepatocellular Cancer (FLC)
- 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.
DNAJB1-PRKACA peptide vaccineDrug
Also called Hiltonol® (Poly-ICLC)
- 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.
- Drug: 0.3 mg DNAJB1-PRKACA peptide vaccine + 0.5mg Poly-ICLC
NivolumabDrug
Also called OPDIVO
- 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.
- Drug: 3mg/kg and 480mg IV
IpilimumabDrug
Also called YERVOY®
- 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.
- Drug: 1mg/kg IV
| Study group | Role | What they receive |
|---|---|---|
| DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab | Experimental | Cohort A: Patients with FLC cancer with no prior checkpoint inhibitor treatment. Cohort B: Patients with FLC cancer with prior checkpoint inhibitor treatment. Cohort C: Patients with non-FLC cancer (solid tumors) with prior checkpoint inhibitor treatment eligible. Receives: Drug: DNAJB1-PRKACA peptide vaccine; Drug: Nivolumab; Drug: Ipilimumab |
| R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab | Experimental | 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. Re-enrolling patients who come off treatment ≤ 12 months from last dose may resume therapy at the study timepoint that they stopped study therapy. Patients who came off study therapy > 12 months of last dose (i.e. to pursue alternative therapies (for example, surgical debulking), or after completion of the 2 years of study therapy), may restart study therapy at C1D1. In both cases, if the investigator assesses a drug-related toxicity to be related to anti-CTLA4 (ie. not anti-PD(L)1) therapy, patients can be enrolled in the study with nivolumab plus FLC peptide vaccine only. Receives: Drug: DNAJB1-PRKACA peptide vaccine; Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
All Cohorts: Number of participants experiencing study drug-related toxicities
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
Measured: 4 years
All Cohorts: Fold change in interferon-producing DNAJB1-PRKACA-specific CD4 and CD8 T cells at 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.
Measured: Baseline and 10 weeks
Cohort A only: Progression-free survival (PFS)
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.
Measured: 6 months
Secondary outcomes (5)
Objective response rate (ORR)
ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Measured: 4 years
Duration of response (DoR)
Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date of disease progression or death is documented per RECIST 1.1. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions.
Measured: 4 years
Disease control rate (DCR)
DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Measured: 4 years
Progression-free survival (PFS)
PFS is defined as number of months from the date of first treatment until first documented local progression or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Measured: 4 years
Overall survival (OS)
OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2020
- Study start20 Apr 2020
- Primary completion1 Mar 2029 (estimated)
- Study completion1 Mar 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Fibrolamellar Hepatocellular Carcinoma (FLC)Studies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Fibrolamellar Cancer Foundation
- Responsible party
- Sponsor
- Investigators
- Mark Yarchoan, MD, Principal investigator, Johns Hopkins Medical Institution
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04248569
- Sponsor's protocol ID
- J19140
- Other IDs
- IRB00222681
- Status last verified
- Dec 2025
- First submitted
- 28 Jan 2020
- Last updated
- 3 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baretti M, Kirk AM, Ladle BH, Kamdar Z, Bendinelli KJ, Ho WJ, Adhikari S, Clark NA, Sundararaman B, Wang H, Kung HC, Hernandez J, Qi H, Shin SM, Hernandez A, Nakazawa M, Schattgen SA, Crawford JC, Furth M, Anders RA, Thoburn C, Zaidi N, Huff AL, Nauroth J, Jaffee E, Pogorelyy MV, Thomas PG, Yarchoan M. A therapeutic peptide vaccine for fibrolamellar hepatocellular carcinoma: a phase 1 trial. Nat Med. 2025 Dec;31(12):4246-4255. doi: 10.1038/s41591-025-03995-y. Epub 2025 Nov 24.
PubMed 41286513Short SS, Kastenberg ZJ, Wei G, Bondoc A, Dasgupta R, Tiao GM, Watters E, Heaton TE, Lotakis D, La Quaglia MP, Murphy AJ, Davidoff AM, Mansfield SA, Langham MR, Lautz TB, Superina RA, Ott KC, Malek MM, Morgan KM, Kim ES, Zamora A, Lascano D, Roach J, Murphy JT, Rothstein DH, Vasudevan SA, Whitlock R, Lal DR, Hallis B, Butter A, Baertschiger RM, Lapidus-Krol E, Putra J, Tracy ER, Aldrink JH, Apfeld J, Le HD, Park KY, Rich BS, Glick RD, Fialkowski EA, Utria AF, Meyers RL, Riehle KJ. Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study. Cancer. 2022 Jul 15;128(14):2786-2795. doi: 10.1002/cncr.34256. Epub 2022 May 13.
PubMed 35561331O'Neill AF, Church AJ, Perez-Atayde AR, Shaikh R, Marcus KJ, Vakili K. Fibrolamellar carcinoma: An entity all its own. Curr Probl Cancer. 2021 Aug;45(4):100770. doi: 10.1016/j.currproblcancer.2021.100770. Epub 2021 Jul 1.
PubMed 34272087
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT04248569
- Acronym / sponsor ID
- J19140
- Keywords
- DNAJB1-PRKACA Peptide Vaccine, Nivolumab, Ipilimumab, Anti-PD-1 (receptor blocking antibody), Anti-CTLA-4 (receptor blocking antibody), Neoantigen Vaccines, Cancer Vaccines, Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Fibrolamellar Cancer Foundation
- Study start
- 20 Apr 2020 (actual)
- Primary completion
- 1 Mar 2029 (estimated)
- Study completion
- 1 Mar 2034 (estimated)
- First posted
- 30 Jan 2020 (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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab | Experimental | Drug: DNAJB1-PRKACA peptide vaccine, Drug: Nivolumab, Drug: IpilimumabCohort A: Patients with FLC cancer with no prior checkpoint inhibitor treatment. Cohort B: Patients with FLC cancer with prior checkpoint inhibitor treatment. Cohort C: Patients with non-FLC cancer (solid tumors) with prior checkpoint inhibitor treatment eligible. |
| R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab | Experimental | Drug: DNAJB1-PRKACA peptide vaccine, Drug: Nivolumab, Drug: IpilimumabRe-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. Re-enrolling patients who come off treatment ≤ 12 months from last dose may resume therapy at the study timepoint that they stopped study therapy. Patients who came off study therapy > 12 months of last dose (i.e. to pursue alternative therapies (for example, surgical debulking), or after completion of the 2 years of study therapy), may restart study therapy at C1D1. In both cases, if the investigator assesses a drug-related toxicity to be related to anti-CTLA4 (ie. not anti-PD(L)1) therapy, patients can be enrolled in the study with nivolumab plus FLC peptide vaccine only. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- 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.
Key exclusion criteria (51 listed)
- 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 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).
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 |
|---|---|---|
| DNAJB1-PRKACA peptide vaccineAlso: Hiltonol® (Poly-ICLC)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 | DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab, R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab |
| NivolumabAlso: OPDIVO1. 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 | DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab, R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab |
| IpilimumabAlso: YERVOY®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 | Drug | DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab, R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab |
Primary outcome
All Cohorts: Number of participants experiencing study drug-related toxicities
Time frame: 4 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 weeks
Time frame: Baseline 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)
Time frame: 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.
5 secondary outcomes
Objective response rate (ORR)
Time frame: 4 years
Duration of response (DoR)
Time frame: 4 years
Disease control rate (DCR)
Time frame: 4 years
Progression-free survival (PFS)
Time frame: 4 years
Overall survival (OS)
Time frame: 4 years
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 3 Dec 2025.
- Derived from this study: PubMed 41286513Baretti M, Kirk AM, Ladle BH, Kamdar Z, Bendinelli KJ, Ho WJ, Adhikari S, Clark NA, Sundararaman B, Wang H, Kung HC, Hernandez J, Qi H, Shin SM, Hernandez A, Nakazawa M, Schattgen SA, Crawford JC, Furth M, Anders RA, Thoburn C, Zaidi N, Huff AL, Nauroth J, Jaffee E, Pogorelyy MV, Thomas PG, Yarchoan M. A therapeutic peptide vaccine for fibrolamellar hepatocellular carcinoma: a phase 1 trial. Nat Med. 2025 Dec;31(12):4246-4255. doi: 10.1038/s41591-025-03995-y. Epub 2025 Nov 24.
- Derived from this study: PubMed 35561331Short SS, Kastenberg ZJ, Wei G, Bondoc A, Dasgupta R, Tiao GM, Watters E, Heaton TE, Lotakis D, La Quaglia MP, Murphy AJ, Davidoff AM, Mansfield SA, Langham MR, Lautz TB, Superina RA, Ott KC, Malek MM, Morgan KM, Kim ES, Zamora A, Lascano D, Roach J, Murphy JT, Rothstein DH, Vasudevan SA, Whitlock R, Lal DR, Hallis B, Butter A, Baertschiger RM, Lapidus-Krol E, Putra J, Tracy ER, Aldrink JH, Apfeld J, Le HD, Park KY, Rich BS, Glick RD, Fialkowski EA, Utria AF, Meyers RL, Riehle KJ. Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study. Cancer. 2022 Jul 15;128(14):2786-2795. doi: 10.1002/cncr.34256. Epub 2022 May 13.
- Derived from this study: PubMed 34272087O'Neill AF, Church AJ, Perez-Atayde AR, Shaikh R, Marcus KJ, Vakili K. Fibrolamellar carcinoma: An entity all its own. Curr Probl Cancer. 2021 Aug;45(4):100770. doi: 10.1016/j.currproblcancer.2021.100770. Epub 2021 Jul 1.
- 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.
Mark Yarchoan, MD principal investigator
Johns Hopkins Medical Institution
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 DNAJB1-PRKACA peptide vaccine, Nivolumab and Ipilimumab in people with Fibrolamellar Hepatocellular Carcinoma (FLC), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
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 23 inclusion and 51 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 3 Dec 2025. 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 United States. 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 Colleen Apostol, RN (410-614-3644, GIClinicalTrials@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All Cohorts: Number of participants experiencing study drug-related toxicities (time frame: 4 years). The study lists 3 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 NCT04248569, which also lists 3 linked publications.
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 3 Dec 2025.