Scientific Publications and Presentations

A pilot study of a DNAJB1-PRKACA fusion kinase peptide vaccine combined with nivolumab and ipilimumab for patients with fibrolamellar hepatocellular carcinoma

November 1, 2023

Baretti, Ladle, Nauroth, Wang, Durham, Thoburn, Ferguson, Thompson, ... , Jaffee & Yarchoan
Abstract presented at the Society for Immunotherapy of Cancer's 2023 annual meeting

In an abstract release for the the 2023 annual meeting of the Society for Immunotherapy of Cancer, the Johns Hopkins University team released the initial results of their peptide vaccine clinical trial launched in 2020. The trial investigated the potential effectiveness of a targeted vaccine against FLC’s DNAJ-PKAc driver when combined with the checkpoint inhibitors nivolumab and ipilimumab.

The vaccine tested was a synthetic peptide 24 amino acids long covering the junction between the HSP40- and PKAc-derived portions of the fusion protein. The FLC patients who participated in the clinical trial all had active, progressive metastatic cancer that was not controlled by systemic therapy. In all cases the presence of the DNAJB1-PRKACA gene fusion was confirmed. The trial subjects received no additional cancer treatment during the trial, and none had been treated previously with an immune therapy such as an ICI.

A major question was whether the treatment would be safe. While some patients suffered adverse events, such as autoimmune reactions, these were within the range expected for treatment with two ICIs and could be managed. A second question was whether patients would mount an immune response against the immunizing peptide vaccine. Out of 12 patients who could be evaluated, 9 generated responses to the vaccine – that is they had substantial numbers of T cells that showed specific immune reactions when exposed to the immunizing peptide.

Finally, 3 of the 12 patients experienced strong clinical benefit – a significant reduction in the size of their tumors.

Click here to read the full abstract from the annual meeting.