A NEW personalised mRNA therapy has significantly improved recurrence-free survival in patients with high-risk melanoma, according to findings from a Phase III trial presented at the European Society for Medical Oncology (ESMO) Congress 2026 today.
The announcement follows an early leak of the data two days prior to the scheduled symposium, which saw stock prices for manufacturers fall rapidly.
The Phase III INTerpath-001 trial, which tested adding the personalised mRNA therapy intismeran autogene to pembrolizumab treatment in patients with surgically resected, stage IIB–IV cutaneous melanoma, showed more that 40% reduction in risk of death or reoccurrence.
The double-blind, randomised study compared the combination with placebo plus pembrolizumab as adjuvant treatment for the disease after surgery.
The findings demonstrate the potential of targeting patient-specific tumour antigens to improve outcomes following surgery for cancer that previously had limited treatment options.
Many patients with high-risk melanoma experience recurrence despite adjuvant therapy. Intismeran is an mRNA-based individualised neoantigen therapy designed to expand existing and generate new antitumour T-cell responses against antigens derived from each patient’s tumour.
The study enrolled 1,137 adults with surgically resected stage IIB/IIC or III/IV cutaneous melanoma and a tumour sample suitable for next-generation sequencing. Participants were randomly assigned in a 2:1 ratio to intismeran plus pembrolizumab or placebo plus pembrolizumab, with 757 and 380 patients allocated to each group, respectively.
Pembrolizumab was administered intravenously at 400 mg every 6 weeks for nine cycles. Patients also received nine intramuscular doses of intismeran 1 mg or placebo every 3 weeks. Pembrolizumab began at randomisation, while intismeran or placebo started upon availability.
The primary endpoint was recurrence-free survival. Secondary endpoints included distant metastasis-free survival, overall survival, and safety.
At the data cut-off of 30 June 2026, median follow-up was 24.6 months. The estimated 24-month recurrence-free survival rate was 82.2% with intismeran plus pembrolizumab, compared with 70.0% with placebo plus pembrolizumab.
The hazard ratio was 0.58 (95% CI: 0.45–0.75; p<0.001), demonstrating a significant improvement with the combination which reduced the risk of recurrence or death by 42% compared with placebo plus pembrolizumab.
Distant metastasis-free survival also improved. At 24 months, estimated rates were 88.5% in the combination group and 80.2% in the control group, with a hazard ratio of 0.62 (95% CI: 0.45–0.85; p=0.002).
The investigators reported similar benefit across stage IIB–IIIB and stage IIIC–IV disease, as well as other subgroups.
Grade 3 or higher adverse events occurred in 23.6% of patients receiving intismeran plus pembrolizumab and 20.3% receiving placebo plus pembrolizumab. Adverse events led to simultaneous discontinuation of both treatments in 6.5% and 5.3%, respectively.
The most common adverse events were pyrexia, injection site pain, and fatigue. Pyrexia occurred in 52.2% versus 8.2%, injection site pain in 51.0% versus 9.5%, and fatigue in 38.5% versus 29.7%.
The investigators concluded that the combination was generally well tolerated and significantly improved both recurrence-free and distant metastasis-free survival.
These findings support the potential of personalised mRNA therapy in adjuvant melanoma treatment, although overall survival results were not reported in the abstract.
Professor Georgina V. Long, lead author of the study, said in a press conference at ESMO that the significance of the findings “cannot be underscored” and that they offer a “new benchmark for adjuvant treatment of melanoma”.
Her colleague, Igne Marie Svane, added that the scope of the treatment is not only limited to melanoma and the “completely new concept” has the potential to be implemented in other cancers in the future.
Despite the success of the trial, the exciting new data was leaked before it’s official scheduled presentation by researchers as part of the Presidential Symposium at the ESMO Congress on Saturday.
The early release of the trial results, which became public through an oncology website two days before the implemented embargo was due to be lifted, spelled trouble for the vaccines manufacturers, Moderna and Merck.
The drugs makers each saw a sharp sell-off after the premature disclosure, with reports that Moderna shares fell approximately 25% during trading, temporarily wiping around $24bn from its market value, while Merck shares were down nearly 1%.
According to analysis, trial results fell short of investors’ high expectations, particularly for reducing distant metastasis or death.
Despite clear significant clinical benefits and optimism from the scientists involved in the study, investors questioned the treatment’s commercial potential and whether its success would extend beyond melanoma.
Reference
Long GV et al. 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). Abstract LBA1. Clinical trial: NCT05933577. ESMO Congress, 23-27 October 2026.
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