A Neoantigen Vaccine for Melanoma?

Harnessing the immune system through a vaccine to prevent recurrence of metastatic cancer has long been a tantalizing but elusive aim in tumor immunotherapy. A number of negative phase 3 studies in the last decade dampened enthusiasm for cancer vaccines, but the tide seems to be turning. Now, investigators present results from the industry-sponsored, phase 2b KEYNOTE-942 trial, the first randomized study of a neoantigen vaccine plus pembrolizumab with a clinical efficacy endpoint.

Leveraging new technology in the form of an mRNA vaccine — that used for the successful COVID-19 vaccine — researchers created a platform to deliver a unique, personalized, cancer-specific neoantigen vaccine (mRNA-4157 [V940]) based on each patients' individual cancer mutations. In the open-label, randomized (2:1) study of 157 patients with high-risk, resected stage III or IV melanoma, those who received the combination of this neoantigen vaccine and pembrolizumab were more likely to be free from recurrent melanoma at 18 months than those who received pembrolizumab alone (79% vs. 62%; two-sided P=0.053). There were no grade 4–5 adverse events associated with the neoantigen vaccine.