Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC))Phase 1NCT07430202

A DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)

A Phase 1 study testing DNAJB1-PRKACA Peptide Vaccine, DRP-104 and Nivolumab in people with Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC)), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

The purpose of this study is to determine whether the combination of a neoantigen vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with DRP-104, Nivolumab and Ipilimumab is safe and yields a clinically compelling antitumor activity measured as based on objective response rate (ORR, assessed by RECIST… Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC))
What is being tested?: DNAJB1-PRKACA Peptide Vaccine, DRP-104 and Nivolumab
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 27 participants
Where: 1 siteUnited States
Study dates: Oct 2026to Oct 2030
Phase: Phase 1

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

Must have histologically confirmed FLC that is metastatic or unresectable.
Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing, DNA-sequencing, or in situ hybridization in the archival tissue.
Must have demonstrated radiographic progression on prior or current immunotherapy.
Age ≥ 12 years.
Patients < 18 years old must have a body weight ≥ 40 kg.
ECOG (Eastern Cooperative Oncology Group) performance status of ≤2

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Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
Patients must have adequate kidney and liver function defined by study-specified laboratory tests.
Must have measurable disease per RECIST 1.1
Willingness to provide tissue and blood samples for mandatory translational research.
Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
For both Women and 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

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.
Must 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.
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 grade 2 fatigue, rash, and endocrinopathy successfully managed hormone replacement therapy, or alopecia or stable neuropathy, unless approved by the IND Sponsor.

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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 attributed to compounds of similar chemical or biologic composition of polyinosinic-polycytidylic acid (Poly-ICLC) and/or DRP-104 and/or nivolumab and/or ipilimumab.
History of severe hypersensitivity reaction to any monoclonal antibody.
Has an active autoimmune disease.
Prior allogeneic stem cell transplantation or organ transplantation.
Has a diagnosis of immunodeficiency.
Systemic corticosteroids at immunosuppressive doses.
Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
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 active medical and/or psychiatric illness/social psychosocial problems that that would limit compliance with study requirements.
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.
Pregnant or breastfeeding.
Has a known history of Human Immunodeficiency Virus (HIV)/AIDS.
Has active hepatitis B. Patients with chronic or acute HBV infection.
Have had evidence of active or acute diverticulitis, intra-abdominal abscess, or GI obstruction which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study.
Unwilling or unable to follow the study schedule for any reason.
Patient is at the time of signing informed consent a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
Evidence of clinical ascites.
Patients with QTc prolongation > 470 ms according to Fridericia formula.
Patients receiving potent inducers of CYP 3A4/5 (including but not limited to apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin and St. John's Wort) who cannot safely discontinue drug at least 14 days prior to Cycle 1 Day 1.
Have had an allergen hyposensitization therapy within 2 weeks prior to initiation of study treatment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Colleen Apostol, RN contact

410-614-3644

GIClinicalTrials@jhmi.edu

United States1 site, 1 recruiting

Johns Hopkins SKCCC
Baltimore, Maryland, 21231
Colleen Apostal, RN, 410-614-3644, GIClinicalTrials@jhmi.edu
Marina Baretti, MD
Recruiting

Other trials in United States

About this study

Official title: A Phase 1b Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab for Patients With Advanced Stage Fibrolamellar Hepatocellular Carcinoma (FLC)

Conditions: Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC))
Being tested: DNAJB1-PRKACA Peptide Vaccine, DRP-104, Nivolumab, Ipilimumab
Keywords: Fibrolamellar Carcinoma (FLC), Liver Cancer, DNAJB1-PRKACA Fusion Kinase Peptide Vaccine, DRP-104 (glutamine antagonist peptide), Nivolumab, Ipilimumab, Immunotherapy, Anti PD-L1 (Anti-Programmed Death Ligand 1), PD-L1 (Programmed Death Ligand 1), Carcinoma, Glutamine antagonist
Medical subject headings: Liver Neoplasms, Fibrolamellar hepatocellular carcinoma, 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)
1. Patients will receive treatment on Day 1, 8 and 15 of cycle 1 and on Day 1 of cycle 2, 3, and 4 (Prime Phase). Boost vaccinations will be administered every 3 cycles beginning from C5D1.
2. Drug: 0.3 mg DNAJB1-PRKACA peptide vaccine + 0.5 mg Poly-ICLC
DRP-104Drug
1. Patients will receive treatment on Day 1, 4, 8, 11, 15, and 18 of cycle 1-4 (Prime Phase) then on Days 1, 4, 8, 11, 15, 18, 22 and 25 of each cycle starting on Day 1 of Cycle 5 (Boost/maintenance Phase). DRP-104 will be administered as a subcutaneous injection twice a week (BIW) on a continuous schedule for up to two years.
2. Drug: 145 mg
NivolumabDrug
Also called OPDIVO
1. Patients will receive treatment on Day 1 of each Cycle. Nivolumab 3mg/kg will be administered every 3 weeks as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycle 1-4 (Prime Phase). Nivolumab infusions will be administered as a flat dose of 480mg every 4 weeks starting on Day 1 of Cycle 5 (Boost/maintenance).
2. Drug: 3mg/kg and 480mg IV
IpilimumabDrug
Also called YERVOY®
1. Patients will receive treatment on Day 1 of Cycle 1-4 (Prime Phase). Ipilimumab (1 mg/kg) will be administered. Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10/+15min).
2. Drug: 1mg/kg IV

Study groups in NCT07430202
Study group	Role	What they receive
Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab	Experimental	Not described Receives: Drug: DNAJB1-PRKACA Peptide Vaccine; Drug: DRP-104; Drug: Nivolumab; Drug: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of participants experiencing grade 3 or above drug-related toxicities
When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v6.0) will be counted only once for a given subject.
Measured: 4 years
Objective response rate (ORR) using immune Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
ORR is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) to DRP-104 in combination with DRP-104, Nivolumab and Ipilimumab, based on the immune Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is >20percent increase in sum of diameters of target lesions, stable disease (SD) is <30percent decrease or <20percent increase in sum of diameters of target lesions.
Measured: 4 years

Secondary outcomes (2)

Progression-free Survival (PFS) number of months according to RECIST (1.1) criteria.
PFS is defined as the number of months from the date of first treatment to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) 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.
Measured: 4 years
Overall survival (OS) of patients treated with study drug combination
OS is defined as the number of months from the first dose of study treatment to death from any cause. (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.

Oct 2026Oct 2030

First posted24 Feb 2026
Study startOct 2026 (estimated)
Primary completionOct 2030 (estimated)
Study completionOct 2030 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC))Studies of the same condition, open and under way.
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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 27 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07430202
Sponsor's protocol ID: J2622
Other IDs: IRB00541955
Status last verified: Oct 2026
First submitted: 18 Feb 2026
Last updated: 5 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No