April 21st was a red letter day for the fibrolamellar community. A patient at the Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins University, Baltimore, MD received the initial treatment of the first experimental therapy aimed to directly target the primary molecular cause of fibrolamellar carcinoma (FLC). When Tucker Davis and friends began the Fibrolamellar Cancer Foundation 10 years ago, almost nothing was known about the basis of this devastating cancer. In 2014 Sanford Simon’s team at Rockefeller University, with the Foundation’s grant support, discovered a gene fusion, DNAJB1-PRKACA, found in the vast majority of FLC tumors. They also identified the resulting chimeric or hybrid protein (“DP”), which is believed to drive the growth of these cancers. Now Mark Yarchoan and colleagues at Johns Hopkins have begun enrolling subjects in a clinical trial of a “peptide vaccine” designed to stimulate a patient’s immune response against the DP driver protein, specifically against the junction between the “D” and “P” segments. This junction should be unique to the patient’s cancer and absent from normal cells. In addition to testing safety of the new therapy, a main goal of the trial is to find out if those who receive the vaccine indeed mount an immune response against DP and whether that leads to destruction of cancer cells. Trial participants also will be treated with two immune checkpoint inhibitors, drugs which can overcome blockades that limit some patients’ immune responses against their cancers.

Bristol-Myers Squibb is providing financial support and donating the checkpoint inhibitor drugs (Opdivo and Yervoy). The Fibrolamellar Cancer Foundation is supporting the study through a grant to Johns Hopkins, with Dr. Yarchoan as Principal Investigator. Information about the clinical trial can be found at https://clinicaltrials.gov/ct2/show/NCT04248569 (“DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma”). Patients who may be interested in the trial should discuss with their physicians whether it is appropriate for them.