Moderna Unveils Promising mRNA-4359 Cancer Antigen Therapy Data in Melanoma Ahead of ESMO 2025

Moderna presented early clinical, safety, and translational data for its investigational cancer antigen therapy mRNA-4359 at the 2025 European Society for Medical Oncology (ESMO) Congress2 4 6 13 14.

mRNA-4359 is an immune-evasion targeted therapy encoding epitopes of PD-L1 and IDO1, designed to induce antigen-specific T cell responses and counter immune escape in melanoma2 9 14.

The Phase 1/2 study enrolled 29 patients with advanced, checkpoint inhibitor-resistant/refractory (CPI-R/R) melanoma who had received prior checkpoint inhibitor therapy2 6 9 13.

Participants received either 400 µg or 1,000 µg mRNA-4359 intramuscularly every three weeks for up to nine doses, combined with pembrolizumab2 9 13.

Overall, the study reported a 24% objective response rate (ORR) and a 60% disease control rate (DCR)2 6 7 13 14.

Among the subgroup of response-evaluable patients with PD-L1+ tumors (TPS ≥ 1%), the ORR reached 67% (6 of 9 patients), with durability data not yet mature (median duration of response not reached)2 7 13 14.

Peripheral antigen-specific T cell responses and novel T cell receptor clones were successfully induced, underscoring proof of principle for the therapy2 9.

The safety profile of mRNA-4359 plus pembrolizumab was consistent across doses, with no new immune-related adverse events observed13 14.

Based on these results, mRNA-4359 has advanced to the Phase 2 stage of the trial2 8 9 13.

PD-L1 expression may serve as a predictive biomarker for response to the therapy in this high unmet need population2 7 14.