Dr Carlino on 5-Year Data With Intismeran Plus Pembrolizumab in Resected Melanoma

“Some translational work in a small subset of these patients found that those T cells were targeting the neoantigens expressed in [intismeran autogene], linking the drug’s mechanism with the improvement in recurrence-free survival.”

Matteo S. Carlino, MBBS, PhD, FRACP, an associate professor and medical oncologist at Westmead and Blacktown Hospitals, a clinical senior lecturer at the University of Sydney, and a member of the melanoma translational research program at Melanoma Institute Australia, discussed 5-year data from the phase 2b KEYNOTE-942 trial (NCT03897881) evaluating the individualized neoantigen therapy intismeran autogene plus pembrolizumab (Keytruda) vs pembrolizumab alone in patients with resected, high-risk stage III/IV melanoma, along with translational findings linking the vaccine’s neoantigen-specific T-cell activity to its clinical benefit.

At a median follow-up of 5 years, the risk of recurrence or death was 49% lower with intismeran autogene plus pembrolizumab compared with pembrolizumab alone (HR, 0.51; 95% CI, 0.29-0.89; one-sided nominal P = .0075), and the risk of distant metastasis or death was 59% lower with the combination (HR, 0.41; 95% CI, 0.20-0.84), according to data presented at the 2026 ASCO Annual Meeting, Carlino noted. The trial randomly assigned 157 patients with resected melanoma 2:1 to intismeran autogene plus pembrolizumab (n = 107) or pembrolizumab alone (n = 50). The benefit reflects the personalized design of the vaccine, which encodes up to 34 neoantigens identified from each patient’s own tumor and is delivered as a lipid nanoparticle–formulated mRNA, according to Carlino.

The second finding Carlino highlighted was translational. Combining intismeran autogene with pembrolizumab produced greater T-cell clonal expansion and more newly detected T-cell clones than pembrolizumab alone, Carlino said. In a companion analysis presented at the same meeting, a subset of these expanded clones was confirmed to recognize neoantigens encoded in the vaccine, providing evidence that intismeran autogene’s mechanism of action, priming neoantigen-specific T cells, underlies the recurrence-free survival benefit seen with the combination, according to Carlino.

Together, the efficacy and translational findings support intismeran autogene plus pembrolizumab as adjuvant therapy following complete resection in high-risk melanoma, Carlino said, and could help inform how individualized neoantigen vaccines are developed across other tumor types going forward, he noted.