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 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)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC))
• Intervention / Treatment: Drug: DNAJB1-PRKACA Peptide Vaccine; Drug: DRP-104; Drug: Nivolumab; Drug: Ipilimumab

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins SKCCC
      • Contact: Colleen Apostal, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
      • Principal Investigator: Marina Baretti, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Drug: DNAJB1-PRKACA Peptide Vaccine; 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.; Drug: 0.3 mg DNAJB1-PRKACA peptide vaccine + 0.5 mg Poly-ICLC; Other Names: Hiltonol® (Poly-ICLC); Drug: DRP-104; 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.; Drug: 145 mg; Drug: Nivolumab; 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).; Drug: 3mg/kg and 480mg IV; Other Names: OPDIVO; Drug: Ipilimumab; 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).; Drug: 1mg/kg IV; Other Names: YERVOY®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	4 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Cancer Research Institute, New York City; Fibrolamellar Cancer Foundation; Dracen Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Marina Baretti, MD, SKCCC • Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: February 18, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Carcinoma; Immunotherapy; Ipilimumab; Liver Cancer; PD-L1 (Programmed Death Ligand 1); Fibrolamellar Carcinoma (FLC); Glutamine antagonist; DNAJB1-PRKACA Fusion Kinase Peptide Vaccine; DRP-104 (glutamine antagonist peptide); Anti PD-L1 (Anti-Programmed Death Ligand 1)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Liver Neoplasms; Fibrolamellar hepatocellular carcinoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Ipilimumab; poly ICLC
• Other Study ID Numbers: J2622; IRB00541955 (Other Identifier: Johns Hopkins Medicine Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No