Moderna presents ‘promising’ early data for cancer antigen therapy

Moderna (MRNA) announced that clinical, safety and translational data from its Phase 1/2 study evaluating mRNA-4359 in combination with pembrolizumab in checkpoint inhibitor-resistant/refractory melanoma patients will be presented at the 2025 European Society for Medical Oncology Congress being held October 17-21. mRNA-4359 is an investigational immune-evasion targeted cancer antigen therapy that encodes epitopes of two common immune escape pathways, PD-L1 and IDO1, to elicit antigen-specific T cell responses that may directly kill tumor cells and deplete tumor suppressor cells. The presentation includes data from 29 participants with CPI-R/R melanoma who have had greater than or equal to1 prior checkpoint inhibitor therapy. Participants received the combination therapy at 400 microgram or 1,000 microgram, given intramuscularly every three weeks for up to nine doses. Across all evaluable patients, the objective response rate was 24% and disease control rate, or the combination of patients achieving tumor response and stable disease, was 60%. Among those with response-evaluable disease and PD-L1+ tumors, the ORR was 67%, with treatment successfully inducing peripheral antigen-specific T cell responses and novel T cell receptor clones. The median duration of response was not reached. “The improved efficacy in PD-L1+ patients supports PD-L1 as a potential predictive biomarker in this high unmet need population,” the company stated. “While early, today’s mRNA-4359 melanoma data in highly CPI-refractory metastatic patients are unique in the field and incredibly promising for future development options. We are encouraged by its potential to address such a high unmet need for many patients. Where other checkpoint inhibitors restore non-specific T cell activity, mRNA-4359 encodes two critical immune escape pathways to help generate new, target-directed T cells. This could enable broader and more durable immune responses for patients who have not had success with prior lines of therapy. We are proud to present these data and to demonstrate the role our mRNA-based therapies could play in transforming the lives of those affected by cancer,” said Dr. Kyle Holen, Head of Development, Therapeutics and Oncology, Moderna.