Moderna, Inc. reports early Phase 1/2 data showing 83% response rate for mRNA-4359 plus pembrolizumab in advanced melanoma.
Written By: Chikkula Pavan Kumar PharmD
Reviewed By: Pharmacally Editorial Team
Moderna, Inc. reported interim data from a Phase 1/2 clinical study evaluating its investigational mRNA-based cancer therapy, mRNA-4359, in combination with pembrolizumab in patients with locally advanced or metastatic melanoma.
The findings, presented at the American Association for Cancer Research Annual Meeting in April 2026, are based on a Phase 2 dose-expansion cohort ((NCT05533697) involving 12 participants receiving the combination as a first-line treatment.
The combination demonstrated an overall response rate of 83%, including two complete and eight partial responses, along with a disease control rate of 92%. The median time to response was six weeks. Clinical activity was observed across PD-L1 expression subgroups, with response rates of 88% in PD-L1 positive tumors and 67% in PD-L1 negative tumors.
Biomarker analyses showed antigen-specific T-cell responses and expansion of novel T-cell receptor clones in all evaluable patients, supporting the therapy’s proposed mechanism of enhancing immune targeting of tumor cells.
The safety profile was described as manageable, with no new immune-related adverse events reported. These findings build on earlier data from 2025 in checkpoint inhibitor-resistant or refractory melanoma, where the combination showed lower response rates but similar trends of improved outcomes in PD-L1 positive patients.
According to Moderna’s Chief Development Officer David Berman, the results, though based on a small cohort, indicate encouraging clinical activity and support further evaluation of mRNA-4359 in melanoma.
Study investigator Dr. Pavlina Spiliopoulou also noted that the observed T-cell activation provides early evidence that mRNA-based approaches may help direct the immune system against cancer in a targeted manner.
mRNA-4359 is designed to encode epitopes from PD-L1 and IDO1, enabling a dual mechanism that targets tumor cells while reducing immunosuppressive elements within the tumor microenvironment.
The U.S. Food and Drug Administration has granted Fast Track designation to the combination for PD-L1 positive unresectable or metastatic melanoma that is refractory to checkpoint inhibitors, supporting expedited development in this setting.
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About the Writer
Chikkula Pavan Kumar, Pharm.D is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.