Early-Stage Data from mRNA-4359 in Melanoma Reveals Encouraging Efficacy in Toughest Cases
Moderna has revealed results from its Phase 1/2 study of mRNA-4359, an immune-evasion targeted cancer antigen therapy, in combination with pembrolizumab. Presented at the 2025 European Society for Medical Oncology (ESMO) Congress, the data focus on patients with advanced, checkpoint inhibitor-resistant or refractory (CPI-R/R) melanoma—a group that historically faces limited options and poor outcomes.
Objective Response Rate Reaches 67% for PD-L1+ Patients: Key Numbers Stand Out
Among 29 participants, who previously received at least one line of checkpoint inhibitor therapy, the combination of mRNA-4359 and pembrolizumab delivered an overall objective response rate (ORR) of 24% and a disease control rate (DCR) of 60%. However, the highlight came from the PD-L1 positive subgroup: among the nine response-evaluable patients whose tumors had PD-L1 expression (TPS = 1%), the ORR soared to 67%. Notably, the median duration of response (DOR) was not yet reached, suggesting potential for long-lasting benefit.
| Patient Subgroup | Number of Patients | Objective Response Rate (ORR) | Disease Control Rate (DCR) | Median Duration of Response (DOR) |
|---|---|---|---|---|
| All Participants | 29 | 24% | 60% | Not Reached |
| PD-L1+ (TPS = 1%) | 9 | 67% | - | Not Reached |
Mechanism Suggests Broader and More Durable Immune Response
mRNA-4359 targets both PD-L1 and IDO1, two key immune escape pathways that tumors exploit to evade attack. By encoding epitopes from both targets, this therapy aims to generate new, highly specific T-cell responses to both kill tumor cells directly and deplete immunosuppressive cells within the tumor environment. This dual mechanism may allow the immune system to mount a broader and more sustained assault, particularly in patients who did not benefit from standard immunotherapies.
Safety Profile Remains Manageable as Phase 2 Continues
Moderna reported that mRNA-4359 in combination with pembrolizumab was generally well-tolerated, with no new immune-related adverse events emerging in this early cohort. As the trial progresses into its Phase 2 portion, ongoing evaluation will further clarify long-term safety and potential broader application, including trials in non-small cell lung cancer.
PD-L1 Emerges as a Potential Biomarker in This High Unmet Need Population
The striking response in PD-L1+ patients is not only encouraging, but it also supports the development of PD-L1 as a predictive biomarker for future immunotherapies in this hard-to-treat group. For context, options for PD-L1+ melanoma patients after failure of first-line immunotherapies are extremely limited, making these early findings a reason for optimism.
What’s Next? Investors and Analysts Can Tune Into Moderna’s Live Webcast
To keep stakeholders updated, Moderna will host an investor and analyst webcast on October 17, 2025, following the ESMO presentation. Details can be found in the Events and Presentations section of Moderna’s investor relations website, with a replay available for at least 30 days.
Bottom Line: Early Signs of a Turning Point for Refractory Melanoma
While these results are early and come from a small group, the high response rate in PD-L1+ melanoma—especially where most options have failed—underscores why the oncology field is watching mRNA-4359 closely. With Phase 2 ongoing, both the potential clinical impact and future business developments warrant attention. If you’re interested in immuno-oncology innovation or emerging cancer therapies, Moderna’s mRNA-4359 could be one to keep on your radar.
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