A new clinical trial shows that combining an experimental mRNA vaccine with immunotherapy reduced the chance of melanoma recurrence or death by 44% compared to immunotherapy alone.
A randomized phase 2b trial, led by researchers at NYU Langone Health and its Perlmutter Cancer Center, included patients who underwent surgery to remove melanoma from a lymph node or other organ and had a recurrence at a site distant from the original cancer. Men and women at high risk of .
Of 107 subjects injected with both an experimental vaccine called mRNA-4157/V940 and the immunotherapy pembrolizumab, 20 of 50 had cancer, compared with 24 within 3 years of follow-up. Of the subjects (22.4%) who relapsed (40%) received pembrolizumab alone.
“Our phase 2b trial showed that using a neoantigen mRNA vaccine in combination with pembrolizumab prolonged recurrence- and death-free time compared to pembrolizumab alone.” Perlmatter Cancer Center.
Results from the Phase 2b trial will be presented on April 16 at the American Association for Cancer Research Annual Meeting in Orlando, Florida.
Randomized phase 3 trials test whether one treatment is better than the current standard of care, while phase 2 trials like the current study test one treatment over another. It provides preliminary reassurance that it is likely to be superior to , leading to large-scale studies to confirm those results. Phase 3 trials of the mRNA-4157/V940 vaccine in combination with pembrolizumab versus pembrolizumab alone are already planned at NYU Langone and many other medical centers around the world, said Laura and Isaac of the same department. He is Professor Perlmutter, said Dr. Weber. M.D. from New York University Grossman School of Medicine.
The results of the study so far led the US Food and Drug Administration (FDA) to grant Breakthrough Therapy designation to mRNA-4157/V940 in combination with pembrolizumab in February.
Our results highlight the role of immune system T cells that can attack viruses as well as cancer. To spare normal cells, this system uses “checkpoint” molecules on her T cell surface to “turn off” attacks on viruses when they clear infection. The body may perceive a tumor as abnormal, but cancer cells hijack checkpoints to switch them off, evade them, and evade the immune response. Immunotherapy, like pembrolizumab, seeks to block checkpoints that make cancer cells more “visible” and re-vulnerable to immune cells.
Immunotherapy has become a mainstay of melanoma treatment, but it is not effective in all patients because melanoma cells, known for their ability to evade the immune system, can become resistant to immunotherapy. For this reason, researchers have considered adding vaccines. Most vaccines in use today are designed to prevent infection, but they can also be tailored to target proteins involved in cancer.
Similar to the COVID-19 vaccine, mRNA-4157/V940 is based on messenger RNA. Messenger RNA is the chemical cousin of DNA that provides the cell with instructions to make proteins. mRNA cancer vaccines are designed to make the body’s immune system recognize cancer cells as different from normal cells. When designing a vaccine against melanoma, researchers tried to provoke an immune response against specific abnormal proteins called neoantigens made by cancer cells.
Because all study volunteers had their tumors resected, the researchers were able to analyze cells for neoantigens specific to each melanoma and create an individualized vaccine for each patient. T cells specific for the neoantigen protein were generated. These T cells can attack melanoma cells trying to grow or spread.
Scientists involved in the study say the personalized mRNA-4157/V940 vaccine took about six to eight weeks to develop for each patient and was able to recognize as many as 34 neoantigens. The most common vaccine-specific side effect reported by patients, which was similar between the two arms of the study, was fatigue.
Original: Addition of new type of vaccine to main immunotherapy dramatically reduces melanoma recurrence
Than: NYU Langone Medical Center
