Phase III studies of a personalized vaccine plus immunotherapy for melanoma have been launched at cancer centres around the world, according to news sources. These trials will involve patients who have had high-risk melanomas (stage IIB to IV) resected, and are based on significant Phase IIb trial outcomes presented at the annual meeting of the American Association for Cancer Research in Orlando on April 16. The vaccine mRNA-4157/V940 was developed by Moderna and Merck, and builds on Moderna’s mRNA research that created the Covid-19 vaccine. Merck also developed the immunotherapy treatment used in the combination, pembrolizumab.
Phase II study results, published in The Lancet, showed a 44% reduction in the risk of recurrence or death in the vaccine plus immunotherapy group after three years compared to the immunotherapy alone, leading to the quick adoption of the Phase III trials. These results led the U.S. Food and Drug Administration in February to grant Breakthrough Therapy Designation to mRNA-4157/V940 in combination with pembrolizumab immunotherapy, a designation designed to speed government reviews of trial outcomes.
Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, of the 107 study subjects who were injected with both the experimental vaccine and the immunotherapy pembrolizumab, the cancer returned in 24 subjects (22.4%) within three years of follow-up, compared to 20 out of 50 patients (40%) who received only pembrolizumab.
“Our phase 2b study shows that a neoantigen mRNA vaccine, when used in combination with pembrolizumab, resulted in prolonged time without recurrence or death compared with pembrolizumab alone,” said study senior investigator Jeffrey S. Weber, MD, PhD, the deputy director of Perlmutter Cancer Center at NYU Langone in New York City, in a press release.
In the U.K., one site for the Phase III trial is University College London Hospital (UCLH) which has received support from the UK Vaccine Innovation Pathway (VIP).
Dr. Heather Shaw, a Consultant Medical Oncologist at UCLH and national U.K. coordinating investigator of the trial, said in a news release: “The idea behind this immunotherapy is that, by prompting the body to make these proteins, it can prepare the immune system to quickly identify and attack any cancer cells bearing them, with the aim of preventing recurrence of melanoma.”
According to researchers, participants will know they have received the standard treatment but will not know if they have received the mRNA treatment.
Tumours from each patient are analyzed to create a personalized mRNA-4157/V940 vaccine that takes about six to eight weeks to develop for each patient. Severe side effects were similar between the two arms of the study, the authors said, with fatigue being the most common side effect specific to the vaccine reported by patients.