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Fusion Kinase Peptide Vaccine Combined with DRP-104, Nivolumab and Ipilimumab

Trial snapshot

  • Formal name: DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined with Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab in Patients with Advanced Stage FLC
  • Trial type: Specifically designed for fibrolamellar carcinoma
  • Phase: Phase I
  • Recruitment status: Active, recruiting
  • Eligible ages: 12+
  • Location: Baltimore, MD (Johns Hopkins – Sidney Kimmel Comprehensive Cancer Center)
  • ClinicalTrials.gov ID: NCT07430202

Overview

Fibrolamellar carcinoma (FLC) is driven in almost every patient by the same genetic abnormality – the fusion of two genes called DNAJB1 and PRKACA. This fusion creates an abnormal protein that is found in FLC cancer cells but not in normal tissue, making it an attractive target for immunotherapy.

This clinical trial NCT07430202 builds on encouraging results from an earlier Johns Hopkins vaccine study. Researchers are testing whether adding a drug called DRP-104 to the vaccine and standard immune checkpoint inhibitors can improve anti-tumor immune response and help more patients achieve tumor shrinkage.

What is being tested?

Patients in this study will receive a combination of four treatments:

  1. DNAJB1-PRKACA peptide vaccine – a vaccine designed to teach the immune system to recognize the abnormal fusion protein that drives FLC. It contains a small piece (a peptide) of the abnormal fusion protein created by the cancer.
  2. Nivolumab – an immune checkpoint inhibitor that takes the brakes off the immune system, allowing T cells (a type of immune cell) to recognize and attack cancer cells more effectively. It works by blocking a protein called PD-1, which tumors often use to hide from the immune system.
  3. Ipilimumab – another checkpoint inhibitor that stimulates immune responses through a different pathway. It steps on the immune system’s gas pedal, helping T cells become more activated and multiply. It works by blocking a protein called CTLA‑4, which normally acts as an early brake on immune responses
  4. DRP-104 – an investigational drug that blocks how tumors use glutamine, an important nutrient. FLC tumors consume glutamine and release toxins (like ammonia) that create a hostile environment that weaken T cells. By blocking tumors’ glutamine metabolism, DRP-104 may slow tumor growth, make the tumor environment less suppressive, and allow immune cells to function better.

What are researchers hoping to learn?

The primary goal is to determine whether this four-drug combination is safe and whether it produces meaningful anti-tumor activity. Researchers will measure:

  • Side effects and tolerability of the drug combination.
  • Objective response rate (how many patients experience significant tumor shrinkage).
  • Progression-free survival (how long cancer remains controlled).
  • Overall survival.

In simple terms, the study is asking:

Can we make the experimental FLC vaccine work better by changing the tumor environment in ways that give immune cells a better chance to attack the cancer?

Why this trial exists: results of the earlier vaccine study (NCT04248569)

The predecessor trial, NCT04248569, was a clinical study of the DNAJB1‑PRKACA vaccine in combination with nivolumab and ipilimumab. Its primary goals were to evaluate safety and determine whether an anti-cancer vaccine could generate a targeted T-cell response against FLC.

For that trial, the JHU team created an “off-the-shelf” vaccine containing a small piece of the unique DNAJB1‑PRKACA fusion protein. Because nearly all FLC tumors contain the same fusion, a single vaccine could potentially be used across most patients with FLC.

The vaccine is intended to train the immune system—especially T cells—to recognize cells carrying the fusion protein and attack them. Checkpoint inhibitors were added to the therapy to help those T cells function more effectively.

Results of the earlier clinical trial were published in Nature Medicine in November 2025. As summarized in that publication:

  • The vaccine appeared safe.
  • About 75% of patients developed the desired immune response.
  • Every patient who mounted that immune response achieved at least some period of disease control.
  • Approximately one-third of responders experienced dramatic and durable tumor shrinkage.
  • Those patients have remained cancer-free several years after treatment.

These findings are especially notable because advanced FLC has historically been very difficult to treat, and durable complete or near-complete responses are rare. However, not every patient responded. Researchers believe one reason may be that the tumor microenvironment in FLC suppresses immune cells and causes T-cell “exhaustion.” By adding the drug DRP‑104 to the combination, researchers are hoping to increase the number of patients who benefit from the targeted immune therapy.

Trial eligibility

This trial will enroll patients 12 years old and older with advanced, unresectable, or metastatic FLC whose tumors contain the DNAJB1-PRKACA fusion. Participants must have experienced disease progression despite prior treatment. Patients with a history of prior treatment with checkpoint inhibitors cannot participate in the study. The study’s principal investigator is Dr. Marina Baretti. More detail can be found at: https://clinicaltrials.gov/study/NCT07430202.

Trial contact information:

Please visit clinicaltrials.gov for a comprehensive list of active trials. 

The Fibrolamellar Cancer Foundation does not provide medical advice.  We provide website users with information to help them better understand their health conditions and current approaches towards diagnosis, treatment and supportive care. Always seek the advice of your physician or other qualified healthcare provider.