AACR 2026 | mRNA-4359 and pembrolizumab shows activity in advanced melanoma

This was a phase one trial, arm 2A, of mRNA vaccine, mRNA-4359, which is designed as a fixed vaccine to target PD-L1 and IDO in patients with locally advanced or metastatic melanoma that were previously untreated in the metastatic setting. There were 12 patients in this study, 10 of whom had cutaneous or unknown primary melanoma, one mucosal and one acral. And promisingly, the first-line data looked quite reassuring with excellent efficacy and good safety. So an objective response rate in this patient population from the mRNA vaccine plus pembrolizumab of 83%, including two out of 12 participants with complete responses. And, you know, we really see that that, you know, compares favorably, at least from a small number of preliminary patients with other frontline options for melanoma. These data are exciting, but I think we all need to put in context that this is 12 patients. And so we need to see this in a larger patient population. We are, you know, eagerly awaiting the data from cohort 2C, which combines this vaccine with ipilimumab plus nivolumab, which is probably more an appropriate frontline partner in the frontline metastatic setting. Those data are forthcoming. And so, you know, I think what this is, is a biologic proof of principle that this is, you know, a good approach and the safety data looked quite reassuring. And that then feeds what is the next study? So is that an expansion with single agent pembrolizumab or another PD-1 partner versus a combination of ipilimumab plus nivolumab or nivolumab plus relatlimab. You know, I think there are many places to go with this. Also, of course, looking forward to seeing the data in the refractory setting as well. The frontline data look quite promising.

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