Moderna and Merck Announce New 3-Year Data for mRNA-4157 Combined With Pembrolizumab for High-Risk Stage III/IV Melanoma

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Moderna and Merck recently announced new results from a planned analysis from the phase 2b randomized KEYNOTE-942 clinical trial (NCT03897881) evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy, in combination with pembrolizumab (Keytruda), Merck’s anti-PD-1 therapy, in patients with resected high-risk stage III/IV melanoma following complete resection (n=157). After a median follow-up of 3 years (34.9 months), adjuvant treatment with mRNA-4157 in combination with pembrolizumab continued to show a clinically meaningful and durable improvement in the primary end point of recurrence-free survival (RFS), reducing the risk of recurrence or death by 49% (HR [95%CI], 0.510 [0.288–0.906]), compared with pembrolizumab as monotherapy.¹

The combination of mRNA-4157 and pembrolizumab also demonstrated a meaningful improvement in one of the key secondary end points of distant metastasis-free survival (DMFS), compared to pembrolizumab as monotherapy, therefore reducing the risk of developing distant metastasis or death by 62% (HR [95% CI], 0.384 [0.172–0.858]).

The new 3-year data on mRNA-4157 and pembrolizumab was presented at the 2024 American Society of Clinical Oncology Annual Meeting. According to the news announcement, an additional year of follow-up is planned, adding to the earlier analyses of the primary and secondary end points.

Based on continued positive data, Merck and Moderna have initiated a phase 3 randomized clinical trial evaluating mRNA-4157 combined with pembrolizumab as an adjuvant treatment in patients with resected high-risk (stage IIB-IV) melanoma (INTerpath-001, NCT05933577), which is actively enrolling participants.

“We are encouraged by the latest results from the KEYNOTE-942/mRNA-4157-P201 study. These data highlight the sustained benefit in RFS and DMFS of mRNA-4157 (V940) as adjuvant treatment in combination with KEYTRUDA in people with resected high-risk melanoma. Importantly, this benefit was observed across various patient exploratory subgroups, reflecting the potential of mRNA-4157 (V940) for a broad range of these patients,” said Kyle Holen, MD, senior vice president and head of development of therapeutics and oncology at Moderna, in the news release. “These findings reinforce our commitment to advancing this innovative treatment in collaboration with Merck, and we are dedicated to harnessing mRNA technology to potentially transform cancer therapy and improve patient outcomes.”

The previous 2.5-year RFS rate of mRNA-4157 plus pembrolizumab was 74.8%, as compared to 55.6% for pembrolizumab as monotherapy, with the benefit observed across exploratory subgroups.

“The sustained improvements in recurrence-free survival and distant metastasis-free survival observed at approximately three years in the KEYNOTE-942/mRNA-4157-P201 study provide further support of the potential of mRNA-4157 (V940) in combination with KEYTRUDA to help patients with resected high-risk melanoma,” said Marjorie Green, MD, senior vice president and head of oncology and global clinical development at Merck Research Laboratories, in the news release. “We look forward to building on our legacy of turning breakthrough science into medicines that may have a meaningful impact on patients’ lives as we continue advancing our broad clinical development program evaluating this novel approach with Moderna.”

Subgroup Data

Additional data from an exploratory subgroup analysis of KEYNOTE-942 in patients with resected high-risk stage III/IV melanoma following complete resection showed that improvement in RFS was seen with mRNA-4157 plus pembrolizumab compared to pembrolizumab as monotherapy regardless of tumor mutational burden (TMB) or programmed death-ligand 1 (PD-L1) status.

The RFS benefit of mRNA-4157 plus pembrolizumab compared to pembrolizumab as monotherapy was maintained across both TMB high (HR [95% CI], 0.564 [0.253–1.258]), TMB non-high (0.571 [0.245–1.331]), PD-L1 positive (0.471 [0.226–0.979]), PD-L1 negative (0.147 [0.034–0.630]), and circulating tumor DNA (ctDNA) negative (0.207 [0.091–0.470]) subpopulations. Additionally, data could not be collected on ctDNA-positive HR due to the small sample size. There were no significant associations between individual human leukocyte antigen alleles and RFS observed for mRNA-4157 plus pembrolizumab.

The exploratory end point of overall survival (OS) favored mRNA-4157 plus pembrolizumab compared to pembrolizumab as monotherapy, with a 2.5-year OSrate of 96.0% vs. 90.2%, respectively (HR [95% CI], 0.425 [0.114–1.584]). The most common adverse events attributed to mRNA-4157 plus pembrolizumab were fatigue (60.6%), injection site pain (56.7%), and chills (49.0%).

Reference

1. Moderna & Merck announce 3-year data for mRNA-4157 (v940) in combination with KEYTRUDA (pembrolizumab) demonstrated sustained improvement in recurrence-free survival & distant metastasis-free survival versus KEYTRUDA in patients with high-risk stage III/IV melanoma following complete resection. News release. Merck. June 3, 2024. Accessed June 3, 2024. https://www.merck.com/news/moderna-merck-announce-3-year-data-for-mrna-4157-v940-in-combination-with-keytruda-pembrolizumab-demonstrated-sustained-improvement-in-recurrence-free-survival-distant-metastasis-free-su/