MRNA-4157/V940

mRNA-4157/V940 is an mRNA based cancer vaccine encapsulated in solid lipid nanoparticles. The 34 mRNA sequences in mRNA-4157/V940 vaccine were generated by an automated algorithm integrated with workflow based on massive parallel sequencing of tissue generated from cancer patients. As adjuvant therapy, mRNA-4157 monotherapy and in combination with pembrolizumab have been investigated in patients with resected solid tumors (melanoma, bladder carcinoma, HPV negative HNSCC, NSCLC, SCLC, MSI-High, or TMB High cancers). It was also investigated in patients with HNSCC and MSS-CRC.

Clinical development history
mRNA-4157/V940 was initially developed by Moderna starting in 2017. In May 2018, Moderna and MSD (Merck in US) announced collaboration on further development of the investigational agent. In 2019 Moderna and Merck jointly put mRNA-4157/V940 into clinical trials in combination with Merck's cancer immunotherapy drug pembrolizumab in resected stage IIIB-IV melanoma. In December 2022, Moderna and MSD announced that the study met its endpoint and demonstrated superiority. In February 2023, the Food and Drug Administration granted mRNA-4157/V940 breakthrough status. In April 2023, mRNA-4157 in combination with pembrolizumab received Prime Scheme Designation from the European Medicines Agency.

In the 2023 AACR meeting, Professor Jeffrey S. Weber, the deputy director of the Perlmutter Cancer Center, presented the primary analysis outcome from the open-label, 2:1 randomization phase 2b study. At the pre-specified analysis point when 42 Recurrence-free survival (RFS) events occurred among 157 participants with resected stage IIIC-IV melanoma, 22.4% (24/107) in the mRNA-4157 plus pembrolizumab arm had recurrent disease, and 40% (20/50) in the pembrolizumab arm had recurrent disease, which lead to the well-known saying: mRNA-4157 in combination with pembrolizumab reduced risk by 44% in surgical resected melanoma.

In July 2023, MSD and Moderna initiated the phase III study (study V940-001) evaluating mRNA-4157 in combination with pembrolizumab for adjuvant treatment of patients with resected high-risk stage IIB-stage IV melanoma.

In the meantime, a phase III study of V940 plus Pembrolizumab versus placebo plus pembrolizumab as adjuvant therapy in non-small cell lung cancer patient with resected stage II, IIIA, IIIB (N2) is registered and expected to start at November 2023. Of note, patients received prior neoadjuvant therapy for their current NSCLC diagnosis, or has been treated with any agent directed to stimulatory or coinhibitory T-cell receptor (e.g. PD-1, PD-L1, CTLA-4, et al.) are not allowed to enrolled in the study.

Mechanism of action
mRNA-4157/V940 is an mRNA based cancer vaccine. When administered, it will produce one of several dozen possible abnormal proteins commonly found in cancerous tissues. The production of those proteins is intended to invoke an immune response. mRNA-4157/V940 is given to patients after their tumors have been sequenced and abnormal proteins identified. The drug is then customized to match a patient's tumor, which makes it an example of personalized medicine.