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A vaccine custom-made from each patient's own tumour mutations, given with pembrolizumab after surgery for high-risk melanoma, reduced recurrence by about 44% compared with pembrolizumab alone in a mid-sized randomised trial, the first sign that personalised cancer vaccines can work.
Open-label randomised phase 2b trial of 157 patients with completely resected stage IIIB-IV melanoma randomised 2:1 to mRNA-4157 (V940, intismeran autogene, encoding up to 34 patient-specific neoantigens) plus pembrolizumab or pembrolizumab alone for about a year. Primary endpoint was recurrence-free survival.
Recurrence-free survival HR was 0.56 (18-month RFS 78.6% vs 62.2%) and distant metastasis-free survival HR 0.35, with benefit regardless of tumour mutational burden or PD-L1. Toxicity was mainly injection-site reactions and flu-like symptoms. It triggered the phase 3 INTerpath-001 trial and a wave of investment in individualised neoantigen vaccines.
For the first time a randomised trial suggests that a vaccine tailored to an individual's tumour can reduce relapse when combined with immunotherapy, which is a proof of concept for a field that had failed for decades. Nothing changes for patients yet: the trial was small, the confidence interval crossed one, and the phase 3 trial in melanoma (and parallel trials in lung and other cancers) must confirm it. If it does, personalised mRNA vaccines could become a routine adjunct to checkpoint inhibitors after surgery.
Shares INTerpath-001 (V940-001), Intismeran autogene, Neoantigen, Tumour mutational burden (TMB).
Shares INTerpath-001 (V940-001), Moderna, Neoantigen, Personalised neoantigen (mRNA) vaccines.
Shares Moderna, Intismeran autogene, Neoantigen, Personalised neoantigen (mRNA) vaccines.
Shares INTerpath-001 (V940-001), Intismeran autogene, Personalised neoantigen (mRNA) vaccines, Melanoma.
Shares Intismeran autogene, Personalised neoantigen (mRNA) vaccines, Merck & Co. (MSD), Melanoma.
Shares Moderna, Intismeran autogene, Neoantigen, Personalised neoantigen (mRNA) vaccines.
Shares Intismeran autogene, Personalised neoantigen (mRNA) vaccines, Merck & Co. (MSD), Pembrolizumab.
Shares Intismeran autogene, Personalised neoantigen (mRNA) vaccines, Merck & Co. (MSD), Pembrolizumab.