In June 2024 Moderna and Merck announced the first presentation of results from a planned analysis from the Phase IIb randomised KEYNOTE-942/mRNA-4157-P201 study. The study evaluates mRNA-4157 (V940) in combination with KEYTRUDA in patients with resected high-risk melanoma (stage III/IV) after complete resection. Moderna states that, with a median follow-up of around three years (34.9 months), adjuvant treatment with mRNA-4157 (V940) in combination with KEYTRUDA “continued to demonstrate a clinically meaningful and durable improvement” in recurrence-free survival (RFS), which was the primary endpoint of the study. Risk of recurrence or death was reduced by 49% when compared with KEYTRUDA alone. The combination also “continued to demonstrate a meaningful improvement” in distant metastasis-free survival (DMFS), reducing the risk of developing distant metastasis or death by 62%.
Study highlights
Data from an exploratory subgroup analysis of the study showed that improvement in RFS was observed in the combination approach compared to KEYTRUDA alone regardless of tumour mutational burden (TMB) or programmed death-ligand 1 (PD-L1) status. The RFS benefit of the combination compared to KEYTRUDA alone was maintained across both TMB high, TMB non-high, PD-L1 positive, PD-L1 negative, and circulating tumour DNA (ctDNA) negative subpopulations. ctDNA positive HR was not estimable due to the small sample size. There were “no significant associations” between individual human leukocyte antigen (HLA) alleles and RFS observed for mRNA-4157 (V940) in combination with KEYTRUDA.
“The exploratory endpoint of overall survival (OS) favoured mRNA-4157 (V940) in combination with KEYTRUDA compared to KEYTRUDA alone, with a 2.5-year OS rate of 96.0% vs 90.2%.”
The safety profile of the combination of mRNA-4157 (V940) and KEYTRUDA “remains consistent with the primary analysis” with the most common adverse events being fatigue (60.6%), injection site pain (56.7%), and chills (49.0%).
Encouraging results
Dr Kyle Holen, Moderna’s Senior Vice President and Head of Development, Therapeutics and Oncology, is “encouraged by the latest results”.
“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.”
Dr Holen suggests that the findings “reinforce our commitment to advancing this innovative treatment” with Merck.
“We are dedicated to harnessing mRNA technology to potentially transform cancer therapy and improve patient outcomes.”
Dr Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, commented that the “sustained improvements” identified in the study “provide further support of the potential of mRNA-4157 (V940) in combination with KEYTRUDA to help patients with resected high-risk melanoma”.
“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 programme evaluating this novel approach with Moderna.”
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