Moderna & Merck Reveal 3-Year Data for mRNA-4157 with KEYTRUDA

June 3, 2024 / Moderna and Merck have unveiled the results of a Phase 2b study examining the efficacy of mRNA-4157 (V940) combined with KEYTRUDA in patients with resected high-risk melanoma. Findings from the KEYNOTE-942/mRNA-4157-P201 study, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, reveal significant benefits in terms of recurrence-free survival (RFS) and distant metastasis-free survival (DMFS).

Key Study Outcomes

The study involved 157 patients with resected stage III/IV high-risk melanoma. After complete resection, these patients received either the combination of mRNA-4157 (V940) and KEYTRUDA or KEYTRUDA alone. With a median follow-up of 34.9 months, the combination therapy reduced the risk of recurrence or death by 49% compared to KEYTRUDA alone. Additionally, the risk of distant metastasis or death was lowered by 62% in the combination therapy group. The 2.5-year RFS rate was 74.8% for the combination therapy compared to 55.6% for KEYTRUDA alone.

Expert Insights

Dr. Kyle Holen from Moderna highlighted the sustained benefits observed in both RFS and DMFS, suggesting that mRNA-4157 (V940) could potentially benefit a broad range of patients. Dr. Marjorie Green from Merck added that the three-year data further support the potential of this combination therapy for high-risk melanoma patients, emphasizing Merck's commitment to innovative cancer treatments.

Subgroup Analysis

The study's exploratory subgroup analysis showed that the combination therapy's benefits extended across various patient subgroups, regardless of tumor mutational burden (TMB) or PD-L1 status. Specifically, the RFS benefit was maintained across TMB high, TMB non-high, PD-L1 positive, PD-L1 negative, and circulating tumor DNA (ctDNA) negative subpopulations. Interestingly, the ctDNA positive subpopulation's hazard ratio was not estimable due to a small sample size.

Safety Profile

The safety profile of mRNA-4157 (V940) combined with KEYTRUDA was consistent with the primary analysis. Common adverse events included fatigue, injection site pain, and chills, mostly graded 1-2. Grade 3 fatigue was the most severe, with no grade 4-5 events reported. Immune-related adverse events were similar in both treatment groups.

Ongoing and Future Clinical Development

Building on these promising results, Moderna and Merck have initiated Phase 3 trials for patients with high-risk melanoma (INTerpath-001) and non-small cell lung cancer (INTerpath-002). These trials are actively enrolling participants. Additionally, Phase 2 trials are underway for renal cell carcinoma (INTerpath-004) and urothelial carcinoma (INTerpath-005), along with a Phase 2/3 trial for cutaneous squamous cell carcinoma (INTerpath-007).

About mRNA-4157 (V940)

mRNA-4157 (V940) is an investigational mRNA-based individualized neoantigen therapy designed to target unique mutational signatures in a patient's tumor. By encoding up to 34 neoantigens, the therapy aims to provoke a robust antitumor immune response. KEYTRUDA, an immunotherapy, enhances the body’s ability to detect and combat tumor cells.

About the KEYNOTE-942/mRNA-4157-P201 Study

The ongoing Phase 2b trial enrolled 157 patients with high-risk melanoma. Following complete surgical resection, patients were randomized to receive mRNA-4157 (V940) and KEYTRUDA or KEYTRUDA alone. The primary endpoint is RFS, with secondary endpoints including DMFS and safety. Exploratory endpoints focus on TMB expression and its association with RFS. Currently, an additional 100 patients are being enrolled to gather more data.

Melanoma Overview

Melanoma is the most serious type of skin cancer, characterized by the uncontrolled growth of pigment-producing cells. Over 330,000 new cases were diagnosed globally in 2022. In the U.S., melanoma is a leading cause of skin cancer deaths, with over 100,000 new cases and more than 8,000 deaths expected in 2024.

About KEYTRUDA

KEYTRUDA is a PD-1 therapy that boosts the immune system’s ability to detect and fight tumor cells. It is widely studied across various cancers, with more than 1,600 clinical trials underway. In the U.S., KEYTRUDA is approved for multiple indications, including the treatment of unresectable or metastatic melanoma and as an adjuvant therapy for certain stages of melanoma.

The recent findings from the KEYNOTE-942/mRNA-4157-P201 study mark a significant milestone in melanoma treatment, potentially paving the way for more effective therapies for high-risk melanoma patients.

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