Intismeran autogene plus pembrolizumab versus pembrolizumab alone in high-risk resected melanoma: 5-year update of the randomized phase IIb KEYNOTE-942 study
Author Identifier (ORCID)
Abstract
Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE-942 study (ClinicalTrials.gov identifier: NCT03897881). Eligible patients with resected stage IIIB to IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks. The primary end point was recurrence-free survival (RFS); secondary end points included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), the median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5-76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (hazard ratio [HR], 0.510 [95% CI, 0.294 to 0.887) and DMFS (HR, 0.411 [95% CI, 0.200 to 0.843]), with a favorable trend in overall survival (HR, 0.471 [95% CI, 0.165 to 1.345]) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After a 5-year follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.
Keywords
melanoma, immunotherapy, pembrolizumab, neoantigen, recurrence, oncology
Document Type
Journal Article
Date of Publication
9-10-2026
E-ISSN
15277755
ISSN
0732183X
Volume
44
Issue
26
PubMed ID
42223134
Publication Title
Journal of Clinical Oncology
Publisher
ASCO Publications
School
School of Medical and Health Sciences
Funding Information
Supported by Moderna, Inc, Cambridge, MA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, who are codeveloping intismeran.
Copyright
free_to_read
First Page
2482
Last Page
2489
Recommended Citation
Khattak, A., Carlino, M. S., Meniawy, T., Ansstas, G., Taylor, M. H., Kim, K. B., McKean, M., Long, G. V., Sullivan, R. J., Faries, M., Tran, T. T., Cowey, C. L., Pecora, A., Medina, T., Atkinson, V., Krepler, C., Jemielita, T., Mao, H., Chow, J., . . . Investigators, O. B. O. T. K. (2026). Intismeran autogene plus pembrolizumab versus pembrolizumab alone in high-risk resected melanoma: 5-year update of the randomized phase IIb KEYNOTE-942 study. Journal of Clinical Oncology, 44, 2482–2489. https://doi.org/10.1200/JCO-26-00835