Intismeran plus pembrolizumab improves recurrence-free survival in resected stage IIB to IV melanoma
- **Adding the individualized neoantigen therapy intismeran autogene to pembrolizumab significantly prolonged recurrence-free survival for patients with completely resected high-risk cutaneous melanoma.
- Recurrence-free survival at 24 months was 82.2% in the intismeran-pembrolizumab group and 70.0% in the placebo-pembrolizumab group (two-sided P<0.001).
- The piecewise hazard ratio was 0.99 (95% CI, 0.66 to 1.49) before 6 months and 0.42 (95% CI, 0.30 to 0.58) after 6 months.
- Distant-metastasis-free survival at 24 months was 88.5% with intismeran-pembrolizumab and 80.2% with placebo-pembrolizumab (two-sided P=0.002).
The publication
**Adding the individualized neoantigen therapy intismeran autogene to pembrolizumab significantly prolonged recurrence-free survival for patients with completely resected high-risk cutaneous melanoma. At 24 months, recurrence-free survival was 82.2% with the combination versus 70.0% with pembrolizumab alone in this phase 3 trial.**
Who the findings apply to
The trial enrolled patients with completely resected stage IIB to IV cutaneous melanoma who were randomly assigned in a 2:1 ratio to receive either intismeran or placebo.
Why this matters
The study addresses whether adding a personalized vaccine targeting patient-specific tumor neoantigens can enhance the efficacy of standard adjuvant immunotherapy. The authors concluded that the combination significantly prolonged both recurrence-free survival and distant-metastasis-free survival compared to pembrolizumab alone.
What the study found
Recurrence-free survival at 24 months was 82.2% in the intismeran-pembrolizumab group and 70.0% in the placebo-pembrolizumab group (two-sided P<0.001). The piecewise hazard ratio was 0.99 (95% CI, 0.66 to 1.49) before 6 months and 0.42 (95% CI, 0.30 to 0.58) after 6 months.
Distant-metastasis-free survival at 24 months was 88.5% with intismeran-pembrolizumab and 80.2% with placebo-pembrolizumab (two-sided P=0.002). The piecewise hazard ratio was 1.01 (95% CI, 0.58 to 1.79) before 6 months and 0.50 (95% CI, 0.34 to 0.73) after 6 months.
Adverse events of grade 3 or higher occurred in 23.6% of patients in the intismeran-pembrolizumab group and 20.3% in the placebo-pembrolizumab group. Eight patients (1.1%) in the combination group died from an adverse event, five of whom died before receiving intismeran.
What the result does not establish
The median follow-up was 24.6 months. The benefit appeared after 6 months, with hazard ratios near unity before that time point. Five deaths attributed to adverse events occurred prior to the administration of intismeran in the combination arm.
Authors’ conclusion
“Adjuvant therapy with intismeran plus pembrolizumab significantly prolonged recurrence-free survival and distant-metastasis-free survival as compared with pembrolizumab alone in patients with completely resected, high-risk cutaneous melanoma.”
Trial registration
| Registered title | A Clinical Study of Intismeran Autogene (V940) Plus Pembrolizumab in People With High-Risk Melanoma (V940-001) |
|---|---|
| Registry status | Phase 3, interventional, active not recruiting |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Registered size | 1,089 participants — planned enrolment (estimate). The abstract reports: 1137 patients |
| Where | 165 sites in 26 countries (Argentina, Australia, Belgium, Brazil, Canada, Chile and 20 more) |
| Registered primary outcome |
Primary endpoint named in the abstract: investigator-determined recurrence-free survival, assessed in a time-to-event analysis. Compare the two: a change of primary endpoint after registration matters. |
- Start: Jul 2023
- Paper published: Nov 2026
- Primary completion: Oct 2029 (estimated)
- Completion: Sep 2030 (estimated)
ClinicalTrials.gov record as held by ENCLAI, last updated Sep 2025. The registry status may have changed since; the link shows the current record.
Study and sources
Intismeran Autogene plus Pembrolizumab for Resected Stage IIB to IV Melanoma
Randomised trial · Phase 3 · NEJM · 2026-11-11
Sources and limitations
- PubMed record PMID 43013837 (PubMed / NLM · 2026-11-15)
- Trial registry NCT05933577 (ClinicalTrials.gov · 2026-11-15)
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