Moderna, Merck mRNA Cancer Vaccine Cuts Melanoma Spread

Moderna and Merck announced on June 5, 2024, that their investigational mRNA-based cancer vaccine, Intisemran (mRNA-4157/V940), significantly reduced the risk of melanoma recurrence and spread in patients with high-risk stage III/IV melanoma. The announcement came during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. In the Phase 3 KEYNOTE-942 trial, the combination of Intisemran with Merck's checkpoint inhibitor Keytruda (pembrolizumab) demonstrated a 44% reduction in the risk of disease recurrence or death compared to Keytruda alone. This marks a substantial advancement in the use of mRNA technology beyond infectious diseases into the realm of cancer treatment, building on the success seen with COVID-19 vaccines. Intisemran is a personalized vaccine designed to train the immune system to recognize and attack cancer cells. It is created by sequencing a patient's tumor and identifying up to 34 neoantigens, which are unique mutations present on the surface of cancer cells. The vaccine then instructs the body to produce antibodies against these specific neoantigens. This personalized approach aims to elicit a potent and targeted immune response against the individual's specific cancer. The KEYNOTE-942 trial enrolled 157 patients with stage III/IV melanoma who had undergone complete surgical resection. Patients received Intisemran in combination with Keytruda every three weeks for up to one year, or Keytruda alone. The primary endpoint was recurrence-free survival (RFS). Beyond the 44% reduction in RFS risk, the combination therapy also showed a 65% reduction in the risk of distant metastasis or death in the first two years post-surgery. The safety profile of the combination was consistent with previously observed data for both Intisemran and Keytruda individually, with the most common side effects being injection site reactions. Moderna and Merck are advancing this collaboration, with plans to discuss the next steps with regulatory authorities. This development represents a significant milestone for mRNA therapeutics in oncology, potentially offering a new paradigm for treating various cancers by harnessing the patient's own immune system. The companies are also exploring the potential of this mRNA platform in other cancer types, indicating a broader ambition to leverage this technology in the fight against cancer. The success of Intisemran in this trial could pave the way for its broader adoption and further research into personalized cancer vaccines.