ASCO 2025 | A pilot study of a DNAJB1-PRKACA fusion kinase peptide vaccine combined with nivo and ipi in FLC

Yeah, so here at ASCO this year we presented our results of a pilot study. It was a single center open-label pilot study of a novel peptide vaccine targeting the FLC fusion, the DNAJB1-PRKACA, combined with the dual immune checkpoint blockade, nivolumab and ipilimumab. We enrolled patients that were age 12 and above who had a pathologically proven diagnosis of FLC. Their disease was to be unresectable for the purpose of the study and they had no prior exposure to immunotherapy checkpoint blockade. And in our study they received the vaccine in combination with infusion of nivolumab and ipilimumab. Overall, we enrolled 12 patients that were available for the endpoints of the study. The main endpoint of our work was first to show the safety of this novel approach and this novel vaccine, especially when combined with immunotherapy, but also to see if we could elicit a specific anti-tumor immunity looking at the T cell response against the fusion in the peripheral blood. Of the 12 patients that we enrolled, the median age was around 23, and the majority of patients had received prior treatments, one to four prior lines of therapies. In terms of safety, we found that this approach was very much safe. The most common vaccine-related adverse events were low-grade, usually injection site reaction, fatigue. And then some patients did have a higher grade of toxicity from nivolumab and ipilimumab, but they all resolved with proper management. And we didn’t see grade four or higher type of adverse events. And in terms of the immunological endpoint, when we looked at the T-cell response against the fusion, we saw that at baseline, only one patient had some T-cell response against the fusion but after the vaccination 75 percent of patients achieved this immune recognition of the fusion really suggesting that we were able to boost the immune system against the fusion as well. We also looked at the clinical activity so again these were pretty heavily pre-treated patient populations but in the 12 patients that we treated three patients had a deep and durable response that is maintained as of today, six more patients had a stabilization of their disease. So overall the treatment was associated with a disease control rate of 75%. A big component of our study was to try to better understand where are the factors associated with the response to the vaccine and immunotherapy. And we looked at one of our responders and we looked at, you know, circulating T cell responses in this patient. And so we think that the next, you know, one of the next avenues might be to use adoptive T cell therapy in this type of cancer. But it’s also clear that even though the majority of patients had some immune recognition of the fusion, not all of them had a major clinical response. So we think that perhaps further modulation of the tumor immune microenvironment, perhaps targeting other components of the tumor microenvironment might be needed to elicit a better anti-tumor immunity.