Clinical Summary: 

• The phase 3 INTerpath-001 trial demonstrated a significant improvement in recurrence-free survival with the addition of the individualized neoantigen therapy intismeran autogene to adjuvant pembrolizumab in patients with resected stage IIB-IV melanoma.
• Intismeran autogene plus pembrolizumab also improved distant metastasis-free survival, with an absolute recurrence-free survival benefit exceeding 12% at 2 years.
• The combination did not increase immune-related adverse events or permanent immune-related toxicities compared with pembrolizumab alone, supporting the potential of individualized neoantigen therapy as a new adjuvant treatment strategy.

Matteo Carlino, MD, Westmead Hospital and Melanoma Institute Australia, Sydney, Australia, discusses findings from the phase 3 INTerpath-001 trial. The randomized study evaluated the addition of intismeran autogene, an mRNA-based individualized neoantigen therapy, to pembrolizumab for the adjuvant treatment of patients with resected stage IIB-IV melanoma. Building on earlier phase 2 findings, the trial demonstrated significant improvements in recurrence-free survival and distant metastasis-free survival, with a recurrence-free survival hazard ratio of 0.58 and an absolute benefit exceeding 12% at 2 years.

Dr Carlino emphasizes that the addition of intismeran autogene did not increase the incidence of immune-related adverse events, including permanent immune-related toxicities, compared with pembrolizumab alone. Additional adverse events were primarily transient fever and injection-site pain. He describes INTerpath-001 as a landmark study providing definitive phase 3 evidence supporting the clinical benefit of personalized cancer vaccines. These findings could establish a new approach to adjuvant melanoma treatment and support further investigation of individualized neoantigen therapies across other malignancies.

Transcript:

Hi, my name is Matt Carlino. I'm a medical oncologist from Westmead Hospital and Melanoma Institute Australia. This year at ESMO, my colleague Georgina Long, on behalf of a large group of investigators, presented the results of the phase 3 study INTerpath-001.

INTerpath-001 was a randomized phase 3 study in resected stage II to IV melanoma of adjuvant pembrolizumab plus or minus the personalized neoantigen therapy intismeran autogene. The results of the study built on the previous smaller phase 2 study, finding that the addition of intismeran autogene to pembrolizumab improved both recurrence-free survival and distant metastasis-free survival.

This benefit was significant, with an improvement, a hazard ratio of 0.58 for recurrence-free survival. The absolute benefit at 2 years was over 12%. Importantly, intismeran autogene did not increase the amount of typical toxicities we see with pembrolizumab. There was not an increase in immune-related adverse events and no change in the amount of permanent immune-related adverse events, which are very important to patients. The additional toxicity was minor, consistent with transient fever and injection-site pain.

INTerpath-001 was a landmark study and the first definitive proof of the benefit of personalized cancer vaccines, which will hopefully improve multiple malignancies beyond melanoma.

Source: 

Long GV, Khattak MA, Gogas HJ, 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). Presented at ESMO Congress 2026. October 23-27, 2026; Madrid, Spain. LBA1.