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

NCT07430202 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J2622IRB00541955
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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 1.1). Secondary objectives include progression-free survival (PFS) and overall survival (OS).

Conditions

Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC))

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  4 years

Secondary Outcomes (2)

• Progression-free Survival (PFS) number of months according to RECIST (1.1) criteria.

  4 years

• Overall survival (OS) of patients treated with study drug combination

  4 years

Study Arms (1)

Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab

EXPERIMENTAL

Drug: DNAJB1-PRKACA Peptide Vaccine; Drug: DRP-104; Drug: Nivolumab; Drug: Ipilimumab

Interventions

DNAJB1-PRKACA Peptide Vaccine DRUG

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

Also known as: Hiltonol® (Poly-ICLC)

Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab

DRP-104 DRUG

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

Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab

Nivolumab DRUG

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

Also known as: OPDIVO

Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab

Ipilimumab DRUG

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

Also known as: YERVOY®

Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Dracen Pharmaceuticals, Inc.: collaborator
• Cancer Research Institute, New York City: collaborator
• Fibrolamellar Cancer Foundation: collaborator

Study Sites (1)

Johns Hopkins SKCCC

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Liver Neoplasms; Fibrolamellar hepatocellular carcinoma; Carcinoma

Interventions

poly ICLC; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marina Baretti, MD

  SKCCC • Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostol, RN

CONTACT

410-614-3644; GIClinicalTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: February 24, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)