Moderna and Merck's cancer vaccine intismeran hits both endpoints in Phase 3 melanoma trial
Moderna and Merck (known as MSD outside the US and Canada) announced positive topline results on 19 August 2026 from the pivotal Phase 3 INTerpath-001 trial of intismeran autogene (V940; mRNA-4157) in combination with Merck's Keytruda (pembrolizumab).
In patients with completely resected stage IIB–IV melanoma, the combination met its primary endpoint of recurrence-free survival (RFS) and the key secondary endpoint of distant metastasis-free survival (DMFS) versus Keytruda alone, at a pre-planned interim analysis. The companies characterised it as the first positive Phase 3 readout for an individualised neoantigen therapy and for an mRNA-based cancer therapy — and the first Phase 3 to show a clinically meaningful improvement over Keytruda monotherapy in the adjuvant setting for resected melanoma. Safety was consistent with prior studies, with no new safety signals.
Intismeran is a personalised mRNA vaccine encoding up to 34 neoantigens designed around the unique mutational fingerprint of each patient's tumour. INTerpath-001 (NCT05933577) randomised 1,137 patients 2:1 to the combination versus Keytruda alone. The result builds on Phase 2b KEYNOTE-942 data, where the combination cut the risk of recurrence or death by 49% (HR 0.51) and distant metastasis or death by 59% (HR 0.411). The broader INTerpath programme spans nine Phase 2/3 trials across melanoma, NSCLC, bladder and renal cancer; overall-survival follow-up continues, and the companies plan to present full data at a medical meeting and file with regulators.
Market reaction: Investors treated the readout as a validation of Moderna's post-COVID pivot into oncology. Moderna shares (NASDAQ: MRNA) surged about 177% to roughly $174 on 19 August 2026 — the stock's largest single-day gain on record — more than doubling the company's value, squeezing short sellers to a reported paper loss of around $5.5bn and lifting the year-to-date gain to roughly 445%. Even so, shares remain about two-thirds below their August 2021 peak of $484.
Source: Merck/Moderna press release, 19 August 2026; market data via Bloomberg, 19 August 2026.
