Over the last few years, a team of investigators at Johns Hopkins University conducted an innovative clinical trial designed to test the potential to induce an immune response against fibrolamellar carcinoma with a FLC-specific therapeutic vaccine.

Participants in the clinical trial were given an experimental vaccine containing a peptide (a small segment of a protein) that corresponds to the junction region linking the two parts of the FLC’s chimeric protein. They also simultaneously received two FDA-approved drugs, Opdivo (nivolumab) and Yervoy (ipilimumab), that are designed to enhance the immune response against tumors by overcoming “checkpoint” systems that can limit the immune system’s ability to fight a cancer.

In the video below, Mark Yarchoan, MD and Marina Baretti, MD discuss the results and next steps for that clinical trial – DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined with Nivolumab and Ipilimumab for Patients with Fibrolamellar Hepatocellular Carcinoma. A major question of the study was whether the treatment would be safe. While some patients suffered adverse events, such as autoimmune reactions, they were within the range expected for treatment with two checkpoint inhibitors and could be managed. A second question was whether patients would mount an immune response against the peptide vaccine. Out of 12 patients evaluated, 75% (9) generated robust responses to the vaccine – that is they had generated substantial numbers of T cells that showed specific immune reactions to the peptide.

Finally, what clinical benefits were observed? Importantly, 25% (3) of the patients achieved significant tumor shrinkage/strong partial responses to the treatment. For the other 9 patients, including the three who failed to mount an immune response to the peptide, the FLC tumors did not regress substantially. However, the disease appeared to stabilize in those patients having an immune response to the vaccine.

Achieving three strong, long-lasting clinical responses among 12 subjects is unprecedented in any controlled clinical trial in FLC, or in any anecdotal studies of which we are aware. A key remaining question is why 75% of the study participants had an immune response to the vaccine, but only 25% experienced strong tumor shrinkage. A goal of the Johns Hopkins team is to answer that question and to identify conditions that can help a higher percentage of patients receive a similar therapeutic benefit.

More information about the ongoing trial can be viewed at clinicaltrials.gov (NCT04248569).