INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy (INT) intismeran autogene (intismeran) plus pembrolizumab (pembro) vs pembro alone for adjuvant treatment of resected stage IIB-IV melanoma (MEL)

INTerpath-001

Doente / População Intervenção / Exposição Comparação Desfecho

In patients with resected stage IIB-IV melanoma, intismeran plus pembrolizumab improved recurrence-free survival compared with placebo plus pembrolizumab.

N

1137doentes

Desenho

Double-blind phase 3 trial that randomised 1137 adults with surgically resected stage IIB/IIC or III/IV cutaneous melanoma and a tumour sample suitable for next-generation sequencing 2:1 to intismeran plus pembrolizumab or placebo plus pembrolizumab (NCT05933577).

Desfecho

Recurrence-free survival (RFS).

Resultado24-month RFS rate 82.2% (95% CI 79.3-84.8) with intismeran plus pembrolizumab vs 70.0% (95% CI 65.0-74.5) with placebo plus pembrolizumab. HR 0.58 (95% CI 0.45-0.75; two-sided P <0.001). 24-month distant metastasis-free survival rate 88.5% (95% CI 86.0-90.6) vs 80.2% (95% CI 75.6-84.0). HR 0.62 (95% CI 0.45-0.85; two-sided P 0.002). Grade ≥3 AEs 23.6% vs 20.3%. Discontinuation of both drugs at the same time due to an AE 6.5% vs 5.3%. Pyrexia 52.2% vs 8.2%, injection site pain 51.0% vs 9.5% and fatigue 38.5% vs 29.7%.

Long GV, Khattak MA, Gogas H, et al. Presented at ESMO Congress 2026, abstract LBA1, 24 October. Not yet published.

Discussão e crítica

In this large double-blind trial, adding intismeran to adjuvant pembrolizumab clearly improved recurrence-free and distant metastasis-free survival, and the abstract reports a similar benefit across stage subgroups. Median follow-up is 24.6 months, both reported endpoints are surrogates, and the abstract gives no overall survival data although OS is a secondary endpoint. Pyrexia and injection site pain were far more frequent with intismeran, which may have let patients and investigators work out the allocation despite the placebo. Intismeran was started only once it was available, but the abstract does not report how long manufacture took, how patients fared while waiting or the subgroup hazard ratios.