Leaked Phase III Data Show mRNA Vaccine Improves Melanoma Outcomes
The phase III INTerpath-001 trial found that intismeran autogene plus pembrolizumab improved recurrence-free survival in patients with resected stage IIB-IV melanoma. The combination reduced the risk of recurrence or death by 42% versus pembrolizumab alone, with 24-month recurrence-free survival of 82.2% versus 70%. It also lowered the risk of distant metastasis or death, and the results were released early after an online leak before the scheduled ESMO presentation.
INTerpath-001 randomized 1,137 people after complete melanoma removal in a 2:1 ratio. One group received intismeran autogene—an individualized mRNA therapy encoding up to 34 tumor neoantigens—plus pembrolizumab; the other received placebo plus pembrolizumab. Treatment lasted about a year or until recurrence or toxicity.
The primary analysis found a 42% lower recurrence-or-death risk with the combination (HR 0.58, 95% CI 0.45–0.75; P<0.001). Two-year recurrence-free survival was 82.2% vs 70%. Distant metastasis or death fell 38% (HR 0.62, 95% CI 0.45–0.85; P=0.002), with 24-month rates of 88.5% vs 80.2%. Results leaked before the scheduled ESMO Madrid talk.
If confirmed, these results could alter adjuvant treatment conversations for people with resected stage IIB–IV melanoma and may encourage broader interest in individualized mRNA cancer vaccines. Health systems and manufacturers could face questions about tumor sequencing, bespoke production timelines, and equitable access, while patients may weigh longer-term survival data and side-effect information before adopting a new combination.