What it is
Intismeran autogene is an individualized neoantigen therapy, designed to induce new T-cell responses and expand existing ones against neoantigens specific to each patient's tumour (the trial's registry entry also names it mRNA-4157). In this phase 3, double-blind trial, patients with completely resected stage IIB to IV cutaneous melanoma were randomly assigned to intismeran (1 mg intramuscularly every 3 weeks for nine doses) or placebo, and all received pembrolizumab (400 mg intravenously every 6 weeks for nine cycles). Of 1,137 patients, 757 were assigned intismeran and 380 placebo, and the median follow-up was 24.6 months. At 24 months, recurrence-free survival was 82.2% with intismeran against 70.0% with pembrolizumab alone, and distant-metastasis-free survival 88.5% against 80.2%. There was no apparent difference in the first months: the piecewise hazard ratio for recurrence-free survival (recurrence or death) was 0.99 before 6 months and 0.42 after. Adverse events of grade 3 or higher occurred in 23.6% and 20.3% of the two groups; eight patients in the intismeran group died from an adverse event, five of them before receiving intismeran.
Why it matters
Added to pembrolizumab after melanoma surgery, a therapy built around each patient's tumour neoantigens prolonged recurrence-free survival in a double-blind phase 3 trial. That end point counts both recurrence and death as events. Distant-metastasis-free survival, a key secondary end point, improved as well, with hazard ratios of 1.01 before and 0.50 after 6 months. The authors conclude that adjuvant intismeran plus pembrolizumab significantly prolonged both recurrence-free and distant-metastasis-free survival compared with pembrolizumab alone in completely resected, high-risk cutaneous melanoma.
Underlined numbers link to their source. Every metric and quoted figure is listed under Sources and data below.
Filed underCutaneous Melanoma Detection and Management, Cancer Immunotherapy and Biomarkers, Melanoma and MAPK Pathways
