J Clin Oncol
ASCO 2026: mRNA vaccine combo halves melanoma recurrence
Clinical takeaway: Adding investigational intismeran to adjuvant pembrolizumab produced a durable recurrence and metastasis benefit at five years in resected high-risk melanoma. An ongoing phase 3 trial will determine its role.
Adjuvant pembrolizumab is standard care after resection of high-risk melanoma, but a substantial share of patients still experience recurrence within five years. Whether layering a personalized mRNA neoantigen vaccine on top of checkpoint inhibition would extend protection durably, or fade once treatment ended, had been an open question. The five-year update of KEYNOTE-942 is the longest follow-up yet for this approach.
The recurrence-free survival benefit seen at earlier readouts held. At five years, 68.8% of patients in the combination arm remained recurrence-free, versus 49.1% on pembrolizumab alone, a 49% reduction in the risk of recurrence or death (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29 to 0.89). The combination also cut the risk of distant metastasis by 59% (HR, 0.41; 95% CI, 0.20 to 0.84).
Overall survival, an exploratory endpoint, trended in the same direction. Five-year survival was 92.2% with the combination and 71.3% with pembrolizumab alone (HR, 0.47; 95% CI, 0.17 to 1.35). Seven patients died in each arm, most from disease progression. The wide confidence interval reflects the small trial size and limits how firmly the survival signal can be read.
KEYNOTE-942 randomized 157 patients with resected stage IIIB to IV cutaneous melanoma 2:1 to intismeran plus pembrolizumab or pembrolizumab alone, enrolling in Australia and the United States from 2019 to 2021. Intismeran is built from each patient's tumor sequence, encoding up to 34 neoantigens to prime T cells against residual disease. Patients received nine vaccine doses alongside 18 doses of pembrolizumab. Median follow-up was 60.3 months.
The trial is small and open-label, and overall survival remains a trend rather than a confirmed benefit. The phase 3 INTerpath-001 trial in resected stage IIB to IV melanoma will determine whether the combination earns a place in adjuvant practice. Intismeran is also being tested in lung and other cancers where mutational burden may make neoantigen vaccines viable.
“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,” said senior investigator Janice Mehnert, MD, professor of medicine at NYU Grossman School of Medicine and director of the melanoma medical oncology program at Perlmutter Cancer Center.
She continued, "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."
Source: Carlino MS. J Clin Oncol. 2026 Jun 1. Individualized neoantigen therapy intismeran autogene plus pembrolizumab in resected melanoma: 5-year update of the KEYNOTE-942 study