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KEYNOTE-942: Neoantigen Therapy Plus Pembrolizumab in Resected Melanoma

By: Joshua D. Madera, MD
Posted: Monday, February 12, 2024

The increasing number of patients with cutaneous melanoma who have disease recurrence has led researchers to try to identify effective treatment strategies aimed at reducing recurrence. In the phase IIb KEYNOTE-942 trial, Jeffrey S. Weber, MD, PhD, of the Laura and Isaac Perlmutter Cancer Center at New York University Langone Health, and colleagues assessed the use of the novel mRNA-based individualized neoantigen therapy mRNA-4157 in conjunction with the PD-1 inhibitor pembrolizumab in this patient population. They found that the combination strategy prolonged recurrence-free survival vs pembrolizumab alone in those with high-risk resected melanoma. These findings were published in The Lancet.

“On the basis of the trial results, a phase III registrational study has been initiated ( identifier NCT05933577),” the study authors noted.

From 2019 to 2021, a total of 157 patients with completely resected high-risk cutaneous melanoma were recruited for the study. All patients were required to have had complete surgical excision at least 13 weeks before receiving their first dose of pembrolizumab. They were randomly assigned to receive treatment with open-label mRNA-4157 plus pembrolizumab (n = 107) or pembrolizumab monotherapy (n = 50). Blood and tumor samples were obtained and analyzed using next-generation sequencing.

The study authors reported an improved recurrence-free survival (hazard ratio = 0.561) with mRNA-4157 plus pembrolizumab (22%) compared with pembrolizumab monotherapy (40%). In addition, patients treated with mRNA-4157 plus pembrolizumab had an increased number of grade 3 or higher treatment-related adverse events (25%) compared with pembrolizumab monotherapy (18%). However, the percentage of immune-mediate adverse events was found to be similar for both treatment groups (36%).

“To our knowledge, this study is the first randomized trial to show a clinically significant benefit of an individualized neoantigen therapy approach,” the investigators noted.

Disclosure: For full disclosures of the study authors, visit

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