Significant Improvement in Recurrence-Free and Distant Metastasis-Free Survival
CAMBRIDGE, Mass. and RAHWAY, N.J., June 3, 2024 – Moderna, Inc. (NASDAQ: MRNA) and Merck (NYSE: MRK), known as MSD outside the U.S. and Canada, have announced promising results from a planned analysis of the Phase 2b KEYNOTE-942/mRNA-4157-P201 study. This clinical trial evaluated mRNA-4157 (V940), an investigational individualized neo antigen therapy (INT), in combination with Merck’s anti-PD-1 therapy, KEYTRUDA®, in patients with high-risk stage III/IV melanoma following complete resection. The data reveal a significant and durable improvement in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) compared to KEYTRUDA alone.
Promising Outcomes in Melanoma Treatment
At a median follow-up of 34.9 months, mRNA-4157 (V940) combined with KEYTRUDA reduced the risk of recurrence or death by 49% (HR [95% CI], 0.510 [0.288–0.906]; p=0.019) and the risk of distant metastasis or death by 62% (HR [95% CI], 0.384 [0.172–0.858]; p=0.015) compared to KEYTRUDA alone. The 2.5-year RFS rate for the combination therapy was 74.8%, significantly higher than the 55.6% for KEYTRUDA alone. These benefits were observed across various patient subgroups.
Initiation of Phase 3 and Additional Trials
Building on these results, Moderna and Merck have launched Phase 3 studies in patients with high-risk melanoma and non-small cell lung cancer (NSCLC). Additionally, Phase 2 studies are underway for renal cell carcinoma, urothelial carcinoma, and a Phase 2/3 study for cutaneous squamous cell carcinoma.
Detailed Efficacy and Safety Data
The exploratory subgroup analysis showed consistent RFS improvement with mRNA-4157 (V940) and KEYTRUDA across tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1) status. The combination therapy demonstrated efficacy regardless of TMB high or non-high and PD-L1 positive or negative statuses. The RFS benefit was also maintained in ctDNA negative subpopulations. The 2.5-year overall survival (OS) rate favored the combination therapy (96.0% vs. 90.2%; HR [95% CI], 0.425 [0.114–1.584]).
The safety profile of the combination remained consistent, with the most common adverse events being fatigue (60.6%), injection site pain (56.7%), and chills (49.0%). Most adverse events were Grade 1-2, with no Grade 4-5 events reported. Immune-related adverse events occurred in 37.5% of patients receiving the combination therapy, similar to the 36% observed with KEYTRUDA alone.
Ongoing and Future Clinical Development
Moderna and Merck’s ongoing clinical development programs include the INTerpath-001 and INTerpath-002 Phase 3 trials, which are actively enrolling patients with high-risk melanoma and NSCLC. In 2024, they also initiated the INTerpath-007 Phase 2/3 trial for cutaneous squamous cell carcinoma, INTerpath-004 Phase 2 trial for renal cell carcinoma, and INTerpath-005 Phase 2 trial for muscle-invasive urothelial carcinoma post-radical resection.
About mRNA-4157 (V940) and KEYTRUDA
mRNA-4157 (V940) is an investigational INT that uses synthetic mRNA coding for up to 34 neoantigens, designed based on the unique mutational signature of a patient’s tumor. KEYTRUDA is an immunotherapy that enhances the body’s immune system to detect and fight tumor cells by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
About the KEYNOTE-942/mRNA-4157-P201 Study
The KEYNOTE-942 trial is a Phase 2b randomized, open-label study that enrolled 157 patients with high-risk stage III/IV melanoma following complete surgical resection. Patients were assigned 2:1 to receive mRNA-4157 (V940) and KEYTRUDA versus KEYTRUDA alone. The primary endpoint is RFS, with secondary endpoints including DMFS and safety.
The latest results from the KEYNOTE-942/mRNA-4157-P201 study demonstrate the sustained efficacy and safety of mRNA-4157 (V940) in combination with KEYTRUDA for high-risk melanoma patients. Moderna and Merck are committed to advancing this innovative treatment to potentially transform cancer therapy and improve patient outcomes.
Join TISHHA.
