INTerpath-001 (V940 / mRNA-4157)
After resection of high-risk melanoma, does personalised neoantigen mRNA therapy added to pembrolizumab improve RFS?
One underlying study; aliases and follow-up reports consolidated. Primary discipline: Medical.
1,137 patients with completely resected high-risk stage IIB–IV cutaneous melanoma, randomised 2:1.
Completely resected stage IIB–IV melanoma; the vaccine remains investigational at this evidence cut-off.
1,137 randomised/evaluable as reported.
Individualised intismeran autogene 1 mg every 3 weeks for up to nine doses plus pembrolizumab 400 mg every 6 weeks for up to nine cycles.
Placebo plus pembrolizumab on the same schedule.
Endpoints and results
Primary investigator-assessed RFS; key secondary DMFS, OS, safety, tolerability and QoL.
- Median follow-up 24.6 months; RFS HR 0.58 (95% CI 0.45–0.75; p<0.001).
- 2-year RFS 82.2% vs 70.0%; 2-year DMFS 88.5% vs 80.2% (HR 0.62, 95% CI 0.45–0.85; p=0.002).
- Grade 3–5 treatment-related AEs 14.2% vs 13.4%; OS immature.
- First 6 months showed comparable outcomes; prespecified post-six-month sensitivity analysis showed a larger effect.
Absolute Effect and outcome visualisation
2-year RFS
% recurrence-free at 2 years · 2 years. Bars show reported fixed-time percentages.
Interpretation: RFS difference 12.2 points; approximate landmark NNT 9 at 2 years. Vaccine remains investigational and OS is immature.
Toxicity, discontinuation and quality of life
Trial-specific harms: Grade 3–5 treatment-related AEs 14.2% vs 13.4%; pyrexia 52.2%, injection-site pain 51.0%, fatigue 38.5% with combination.
Treatment burden/discontinuation: Individualised manufacture and up to nine additional injections add logistics and treatment burden.
Quality of life: QoL is a key secondary endpoint; no definitive numerical QoL advantage asserted here.
Subgroups, maturity and limitations
Subgroups: Effects generally consistent across prespecified subgroups; post-six-month effect is sensitivity analysis, not a replacement for ITT primary analysis.
Maturity: ESMO 2026 detailed results announced; OS immature and full peer-reviewed paper not yet independently verified in accessible full text.
Limitations: Regulatory approval not established; distinguish sponsor/meeting results from completed peer-reviewed evidence.
Positive phase III RFS/DMFS findings for a personalised vaccine plus pembrolizumab, but the treatment remains investigational and OS is immature.
Current-practice context must be checked against regional guidelines, patient fitness, biomarkers, alternatives and regulatory status before clinical application. Clinical freshness review and browser-rendered QA remain pending.
Primary sources and registry
Registry: NCT05933577
The Absolute Effect · Updated 26 October 2026 · Never derive NNT from median survival.