The combination of the individualized neoantigen therapy intismeran autogene and pembrolizumab led to an improvement in recurrence-free survival and distant metastasis–free survival rates compared with pembrolizumab alone in patients with high-risk resected melanoma, according to 5-year results from the phase IIb KEYNOTE-942 trial presented at the 2026 ASCO Annual Meeting (Abstract 9500) and simultaneously published in the Journal of Clinical Oncology.
“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 study investigator Janice Mehnert, MD, Professor in the Department of Medicine at NYU Grossman School of Medicine, and Director of the Melanoma Medical Oncology Program and Associate Director of Clinical Research at Perlmutter Cancer Center. “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.”
Background and Study Methods
Intismeran autogene is an mRNA-based vaccine aimed to increasing endogenous neoantigen-specific antitumor T-cell responses.
The phase IIb KEYNOTE-942 trial enrolled 157 patients with high-risk, resected stage IIIB–IV cutaneous melanoma who were randomly assigned to receive either intismeran autogene and pembrolizumab (n = 107) or pembrolizumab alone (n = 50). In the investigational arm, patients received 9 doses of intismeran autogene at 1 mg every 3 weeks and 18 doses of pembrolizumab at 200 mg intravenously every 3 weeks.
The primary endpoint, which was presented previously, was recurrence-free survival, with secondary endpoints of distant metastasis–free survival and safety. All patients completed study treatment before the primary analysis in 2021.
An additional 2 years of follow-up was presented at the ASCO Annual Meeting.
Key Findings
The combination of intismeran autogene and pembrolizumab reduced the risk of recurrence vs pembrolizumab alone by 49% (hazard ratio [HR] = 0.51; 95% CI = 0.29–0.89). At 5 years, the recurrence-free survival rate was 68.8% (95% confidence interval [CI] = 56.3%–78.3%) in the combination arm and 49.1% (95% CI = 33.3%–63.0%) in the monotherapy arm.
The risk of distant metastasis was reduced by 59% with the addition of intismeran autogene (HR = 0.41; 95% CI = 0.20–0.84). Seven patients died during follow-up in each arm.
There was a trend for improved overall survival as well, an exploratory endpoint (HR = 0.47; 95% CI = 0.17–1.35) with 5-year rates of 92.2% (95% CI = 84.2%–96.3%) in the combination arm and 71.3% (95% CI = 35.4%–89.6%) in the pembrolizumab alone arm.
The safety profile for intismeran autogene was considered consistent with prior analyses.
Dr. Mehnert noted that a phase III multicenter trial has already begun to determine the benefit of intismeran autogene in the first-line setting in combination with pembrolizumab for patients with melanoma.
DISCLOSURE: Funding support for this study was provided by Moderna Inc, the manufacturer of intismeran, and Merck & Co, the manufacturer of pembrolizumab. For full disclosures of the study authors, visit coi.asco.org.
