Moderna, Merck Present Promising Trial Data for a Combination of V940 with Keytruda for the Treatment of High-Risk Melanoma Following Complete Resection

Image Credit: Adobe Stock Images/Christoph Burgstedt

Moderna and Merck announced positive results from the Phase IIb KEYNOTE-942/mRNA-4157-P201 trial evaluating Moderna’s novel individualized neoantigen therapy mRNA-4157 (V940) in combination with Merck's Keytruda (pembrolizumab) in patients with high-risk melanoma following complete resection. According to both companies, the combination therapy demonstrated sustained benefits in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) compared to Keytruda alone after three years of follow-up.¹

"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. SVP, head of development, therapeutics and oncology, Moderna, in a press 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 randomized, open-label KEYNOTE-942 trial included 157 patients with high-risk stage III/IV melanoma. After undergoing a surgical resection, participants were randomly assigned to receive V940 (1 mg every three weeks for nine doses) and Keytruda (200 mg every three weeks up to 18 cycles) or Keytruda monotherapy for approximately one year until disease recurrence or unacceptable toxicity. The trial’s primary endpoint was RFS between the time of the first Keytruda dose up until the first reoccurrence. Secondary endpoints included DMFS and safety, with exploratory endpoints that included distribution of tumor mutational burden (TMB) expression in baseline tumor samples across study arms and their association with the primary RFS endpoint.

Investigators found that the combination treatment reduced the risk of recurrence or death by 49% and the risk of developing distant metastasis or death by 62%. These results are a boost from previous data, which demonstrated a 2.5-year RFS rate of 74.8% for the combination therapy versus 55.6% for Keytruda monotherapy. Exploratory subgroup analyses revealed that the RFS benefit extended across different TMB, PD-L1 status, and circulating tumor DNA subpopulations. Additionally, the OS rate after 2.5 years was considerably higher for patients who took the combination therapy compared to Keytruda alone, at 96.2% versus 90.2%, respectively.

The safety profile of the combination treatment has remained consistent with previous parts of the study, with common adverse effects (AEs) such as fatigue, injection site pain, and chills. At the grade of 1-2, the AEs were considered manageable, with immune-related AEs occurring at similar rates between the combination therapy and Keytruda alone.

The data were presented yesterday at the 2024 American Society of Clinical Oncology Annual Meeting, with the study still in progress.¹

"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, SVP, head of oncology, global clinical development, Merck Research Laboratories, in the press 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."

Reference

1. Moderna & Merck Announce 3-Year Data For mRNA-4157 (V940) in Combination With KEYTRUDA(R) (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. Moderna. June 3, 2024. Accessed June 3, 2024. https://investors.modernatx.com/news/news-details/2024/Moderna--Merck-Announce-3-Year-Data-For-mRNA-4157-V940-in-Combination-With-KEYTRUDAR-pembrolizumab-Demonstrated-Sustained-Improvement-in-Recurrence-Free-Survival--Distant-Metastasis-Free-Survival-Versus-KEYTRUDA-in-Patients-With-High-Risk-Stage-IIIIV/default.aspx