Recruiting
Phase 1

Neoantigen Vaccine, DRP-104, Nivolumab, Ipilimumab

Sponsor:

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Code:

NCT07430202

Conditions

Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC))

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Interventions

DNAJB1-PRKACA Peptide Vaccine

DRP-104

Nivolumab

Ipilimumab

Study Details

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))

Study ID

NCT07430202

Start date

Oct, 2026

Status verified date

Oct, 2026

Completion date

Oct, 2030

Anticipated

Primary completion date

Oct, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

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 Design

Enrollment

27 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

Interventions

DNAJB1-PRKACA Peptide Vaccine

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-104

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

Nivolumab

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

Ipilimumab

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

Primary outcome measure

  • Number of participants experiencing grade 3 or above drug-related toxicities [ Time Frame: 4 years ]
  • Objective response rate (ORR) using immune Response Evaluation Criteria for Solid Tumors (RECIST 1.1) [ Time Frame: 4 years ]

Central Contacts and Locations

Central contacts

Colleen Apostol, RN

410-614-3644GIClinicalTrials@jhmi.edu

Locations

Johns Hopkins SKCCC

Recruiting

Baltimore, Maryland, United States, 21231

Contacts

Colleen Apostal, RN

410-614-3644GIClinicalTrials@jhmi.edu

Principal Investigator:

Marina Baretti, MD

More Information

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last update posted

Oct 5, 2026

Last verified

Oct, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-06. This information was provided to ClinicalTrials.gov by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins on 2026-10-05. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.