Phase 3 trials of the combination of the mRNA-4157/V940 vaccine with pembrolizumab versus pembrolizumab alone are already in the works.

Adding an experimental mRNA vaccine to immunotherapy reduced the likelihood of melanoma recurring or causing death by 44% when compared with immunotherapy alone, a new clinical trial shows. 

The phase 2b trial results were presented at the annual meeting of the American Association for Cancer Research in Orlando, FL. The trial included men and women who had surgery to remove melanoma from lymph nodes or other organs and were at high risk for the disease metastasizing to other organs. 

 Of 107 study participants who were ireceived both the experimental vaccine, called mRNA-4157/V940, and the immunotherapy pembrolizumab, the cancer returned in 24 patients (22.4%) within 2 years of follow-up, compared with 20 out of 50 (40%) who received only pembrolizumab.

“Because the study participants all had their tumors removed, their cells were analyzed for molecules that could be recognized by the immune system and were specific to each melanoma, allowing a 'personalized' vaccine to be created for each patient,” says lead study author Jeffrey Weber, MD, PhD, the deputy director of the Perlmutter Cancer Center at NYU Langone Health and the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at NYU Grossman School of Medicine in New York City, NY.  “A larger, confirmatory Phase 3 study is already being planned by Merck and Moderna, which will include patients at NYU Langone and a number of medical centers globally.”

Study results so far led the United States Food and Drug Administration in February to grant Breakthrough Therapy Designation to mRNA-4157/V940 in combination with pembrolizumab.

Immunotherapies have become the mainstay for treating melanoma, although they do not work for all patients as melanoma cells, known for their ability to evade the immune system, can become resistant to immunotherapy. For this reason, researchers have looked at adding vaccines to the protocol. Like the COVID-19 vaccine, mRNA-4157/V940 is based on messenger RNA; mRNA cancer vaccines are designed to teach the body’s immune system to recognize cancer cells as different from normal cells

The personalized mRNA-4157/V940 vaccine took about 6 to 8 weeks to develop for each patient and could recognize as many as 34 neoantigens. Severe side effects were similar between the two arms of the study, they said, with fatigue being the most common side effect specific to the vaccine reported by patients.

The study was funded by Moderna Inc. of Cambridge, Mass., and Merck of Rahway, NJ. mRNA-4157/V940 is being jointly developed and commercialized by Moderna and Merck. Merck is the manufacturer of pembrolizumab. Dr. Weber consults for and has received less than $10,000 per annum from Merck, Genentech, Astra Zeneca, GSK, Novartis, Nektar, Celldex, Incyte, Biond, Moderna, ImCheck, Sellas, Evaxion, Pfizer, Regeneron, and EMD Serono; has received $10,000 to $25,000 from BMS for membership on Advisory Boards; he holds equity in Biond, Evaxion, OncoC4, and Instil Bio; and is on scientific advisory boards for CytoMx, Incyte, ImCheck, Biond, Sellas, Instil Bio, OncoC4, and Neximmune, for which he is remunerated between $10,000 to $50,000 dollars. He is not a member of any speaker’s bureau; NYU received research support from BMS, Merck, GSK, Moderna, Pfizer, Novartis, and Astra Zeneca. Dr. Weber is one of the co-authors on two patents filed by Moffitt Cancer Center and one patent filed by Biodesix and receives less than $6,000 yearly in royalties. These relationships are being managed in accordance with the policies and practices of NYU Langone Health.