Moderna’s mRNA-4359, when used with Keytruda, achieves a 24% overall objective response rate in patients with melanoma, with efficacy increasing to 67% in those positive for PD-L1.
Moderna’s investigational cancer antigen therapy mRNA-4359 elicited “promising” treatment response in a Phase I/II melanoma study when used alongside Merck’s Keytruda, according to data presented Sunday at the 2025 meeting of the European Society for Medical Oncology.
The combo demonstrated a 24% objective response rate (ORR), Moderna reported. These findings come from an analysis of 29 evaluable patients with melanoma who had undergone at least 1 prior line of checkpoint inhibitor treatment. MRNA-4359 was given in 400-µg or 1,000-µg doses intramuscularly every three weeks, up to 9 times in total.
At the time of readout, Moderna had also recorded a 60% disease control rate; that is, 6 of every 10 treated patients achieved tumor response or reached stable disease after treatment.
The combination of mRNA-4359 and Keytruda appeared to be more effective against PD-L1-positive tumors. In a specific subpopulation of patients—those in whom treatment response was evaluable and at least 1% of whose tumor cells expressed the PD-L1 marker—ORR was 67% and the treatment resulted in antigen-specific T cell responses.
In a statement, Kyle Holen, head of Development, Therapeutics and Oncology at Moderna, conceded that Sunday’s findings were “early,” but called them “unique in the field and incredibly promising for future development options.” In particular, Holen noted the ability of mRNA-4359 to induce a target-specific T cell response, whereas typical checkpoint inhibitors trigger nonspecific activity.
According to Moderna, mRNA-4359 is able to elicit such targeted action because it encodes broad epitopes of PD-L1 and the enzyme IDO1, which help tumor cells evade the immune system. This mechanism of action allows mRNA-4359 to not only specifically target cancer cells expressing these markers, but also rebalance the tumor’s environment to allow immune activity.
“This could enable broader and more durable immune responses” in cases where previous therapies have failed, Holen added. Moderna did not specify future development plans for mRNA-4359 in its press announcement, noting only that the asset is in ongoing Phase I/II testing as a monotherapy and in combination with Keytruda in patients with advanced solid tumors. This trial has a completion date of February 2032.
Aside from mRNA-4359, Moderna’s cancer push is anchored by mRNA-4157, a personalized cancer vaccine being developed in partnership with Merck. In December 2023, Phase IIb data showed that the asset, when combined with Keytruda, cut the risk of recurrence or death by 49% in patients with high-risk melanoma who had undergone complete resection. This combo regimen is currently in late-stage development, with launch expected in 2027, according to reporting from Bloomberg in March of this year.
