mRNA-4157 (V940) + Keytruda (pembrolizumab) demonstrated continued improvement in recurrence-free survival and distant metastasis-free survival in high-risk stage III/IV melanoma following complete resection at three years

In this planned analysis occurring with a median follow-up of approximately three years, adjuvant treatment with mRNA-4157 (V940) in combination with Keytruda continued to demonstrate a clinically meaningful improvement in recurrence-free survival (RFS), reducing the risk of recurrence or death by 49% (HR=0.510 [95% CI, 0.288-0.906]; one-sided nominal p=0.0095) compared with Keytruda alone. mRNA-4157 (V940) in combination with Keytruda also continued to demonstrate a meaningful improvement in distant metastasis-free survival (DMFS), compared with Keytruda alone, reducing the risk of developing distant metastasis or death by 62% (HR=0.384 [95% CI, 0.172-0.858]; one-sided nominal p= 0.0077).

“As we continue to follow participants in the KEYNOTE-942/mRNA-4157-P201 study, we are excited to see such a robust clinical benefit with mRNA-4157 (V940) as adjuvant treatment in combination with Keytruda in people with resected high-risk melanoma,” said Kyle Holen, M.D., Moderna’s Senior Vice President and Head of Development, Therapeutics and Oncology. “These data add another positive analysis to the multiple endpoints and subgroups previously assessed in this study. Importantly for this technology, the KEYNOTE-942/mRNA-4157-P201 study was the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and the first combination therapy to show a significant benefit over Keytruda alone in adjuvant melanoma. We look forward to sharing these data with people impacted by this disease and the broader scientific community.”

Adverse events observed with mRNA-4157 (V940) in KEYNOTE-942 remain consistent with those previously reported. At a median planned follow-up of approximately three years, the number of patients reporting treatment-related Grade greater than 3 adverse events were similar between the arms (25% for mRNA-4157 (V940) in combination with Keytruda vs 20% for Keytruda ( alone). The most common adverse events of any grade attributed to mRNA-4157 (V940) were fatigue (60.6%), injection site pain (56.7%), and chills (49%).

In July, Moderna and Merck announced the initiation of a pivotal Phase III randomized INTerpath-001 (V940-001) clinical trial evaluating mRNA-4157 (V940) in combination with Keytruda, as an adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma. Global recruitment in INTerpath-001 has begun NCT05933577). The companies have also initiated a Phase III trial in non-small cell lung cancer that is actively enrolling globally (INTerpath-002,NCT06077760) and plan to expand the development program to additional tumor types.