A personalised mRNA cancer vaccine has shown a lasting benefit for melanoma patients after surgery, with researchers saying it cut the risk of the cancer returning or causing death by 49 percent over five years.
The study, led by researchers from NYU Langone Health, tested the vaccine, called intismeran, alongside pembrolizumab in 107 patients who had their melanoma tumours surgically removed. The results were compared with those from a randomly selected group of 50 patients who received pembrolizumab alone after surgery, which is a current standard of care.
After five years of follow-up, 68.8 percent of patients who received the combination therapy remained cancer free, compared with 49.1 percent of patients in the pembrolizumab-only group.
Researchers said adding intismeran to pembrolizumab also reduced the risk of distant metastasis by 59 percent. Overall survival was 92.2 percent in the vaccine plus immunotherapy group, compared with 71.3 percent in the immunotherapy-only group.
Study senior investigator Janice Mehnert, of NYU Grossman School of Medicine, said: “Our study offers strong evidence to melanoma patients that intismeran vaccine therapy, when used in combination with immunotherapy, can demonstrably reduce their risk of having their cancer return and improve clinical outcomes.
“Our findings also serve as encouragement to cancer researchers globally that mRNA vaccines like intismeran could work well in combination with immunotherapy for other cancers whose high rates of mutations have proven difficult to target.”
Intismeran is a personalised immunotherapy developed using information from a patient’s own tumour. The vaccine is based on messenger RNA, a chemical cousin of DNA that gives cells instructions for making proteins.
Researchers said mRNA cancer vaccines are designed to teach the immune system to recognise cancer cells as different from normal cells. In this study, scientists analysed patients’ removed tumours for 34 neoantigens specific to each melanoma and created a personalised vaccine for each patient.
That process produced T cells specific to the neoantigen proteins encoded by the mRNA, which could then attack melanoma cells trying to grow or spread.
Mehnert said the results highlight the role of T cells, which can attack viruses as well as cancers. She said the immune system uses checkpoint molecules on T cell surfaces to “turn off” their attack against viruses after an infection clears, but cancer cells can hijack those checkpoints to evade immune responses.
Immunotherapies such as pembrolizumab aim to block checkpoints, specifically the PD-1 protein receptor, making cancer cells more visible and vulnerable again to immune cells. Mehnert said PD-1 inhibitors such as pembrolizumab have become the mainstay for treating melanoma, but they do not work for all patients because melanoma cells can become resistant to immunotherapy.
For the KEYNOTE-942 phase 2b trial, patients were enrolled at cancer centres in Australia and the United States from 2019 to 2021. All had surgery to remove their melanoma tumours.
Seven patients in each treatment group died during follow-up, most from cancer. Side effects were considered manageable and included fatigue, pain at injection sites and chills.
The findings are due to be presented next month at the annual meeting of the American Society of Clinical Oncology in Chicago and published at the same time in the Journal of Clinical Oncology.
Mehnert said a phase 3 multicentre trial is already underway to test intismeran with pembrolizumab as a first-line therapy for melanoma. The vaccine is also being tested to see if it can prevent recurrence of lung and other cancers.
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