Cancer Antigen mRNA-4359 Shows Increased Efficacy in Patients with Melanoma

A phase 1/2study (NCT05533697)¹revealed that the cancer antigen therapy mRNA-4359 produced a positive treatment response when paired with pembrolizumab (Keytruda) in patients with melanoma.

The drug combination achieved a 24% overall objective response rate (ORR) and an increased efficacy of 67% in patients positive for PD-L1.² 

There were 29 patients in the study, all of whom 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 3 weeks, up to 9 times in total. Patients also reached a 60% disease control rate, which calculates to 6 of every 10 patients treated achieved tumor response or reached stable disease after treatment.The trial has an estimated completion date of February 2032.² 

“While early, today's mRNA-4359 melanoma data in highly [checkpoint inhibitor]-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," said Kyle Holen, MD,the head of development, therapeutics and oncology at Moderna, in a press release.²"Where other checkpoint inhibitors restore non-specific T-cell activity, mRNA-4359 encodes 2 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."

In a subpopulation of patients whose treatment response was evaluable and at least 1% of whose tumor cells expressed PD-L1, ORR was 67% and resulted in antigen-specific T-cell responses.² 

Patient eligibility criteria included being ≥18 years of age, having histologically confirmed locally advanced or metastatic cancer with measurable disease, and having measurable disease as determined by RECIST v1.1.¹

Exclusion criteria included the patient having active central nervous system tumors or metastases, receiving treatment with prohibited medications or investigational agents within 5 half-lives or 14 days prior to the study, and requiring the use of additional immunosuppression.¹ 

“After failing to respond to first-line immunotherapy, existing options for PD-L1[-positive] patients are limited, underscoring a clear need for effective, tolerable therapies," said David J. Pinato, a clinical professor of experimental cancer therapeutics at Imperial College London, consultant medical oncologist at Imperial College Healthcare NHS Trust, and lead author and presenter of the abstract, in a press release.²"mRNA-4359 has the potential to rebalance the tumor microenvironment to overcome this immunotherapy resistance. These data are encouraging as we continue to investigate the potential of mRNA-4359."

Clinical, safety, and translational data will be presented at the 2025 European Society for Medical Oncology (ESMO) Congress starting on October 17, 2025, in Berlin, Germany.

REFERENCES:

1.Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors. ClinicalTrials.gov. Updated October 8, 2025. Accessed October 15, 2025. https://www.clinicaltrials.gov/study/NCT05533697 

2.Moderna Presents Promising Early Data for Its Investigational Cancer Antigen Therapy at the 2025 European Society for Medical Oncology Congress. News release. Moderna. October 12, 2025. Accessed October 15, 2025. https://tinyurl.com/ta4wwzxz