Adjuvant Intismeran Autogene Plus Pembrolizumab Data Headline Key Melanoma Findings From ESMO 2026

The addition of the individualized neoantigen therapy intismeran autogene to adjuvant pembrolizumab (Keytruda) in patients with resected high-risk melanoma in the phase 3 INTerpath-001 trial (NCT05933577), and the question of how personalized vaccination will fit alongside neoadjuvant immunotherapy, were among the most closely watched melanoma data and trends presented at the 2026 ESMO Congress.

To put some of the most important data to emerge from ESMO 2026 into perspective, OncLive® spoke with experts who shared their insights on the presentations that stood out most to them:

• Dirk Schadendorf, MD, director and chair of the Department of Dermatology at University Hospital Essen and managing director of the West German Cancer Center in Essen, Germany
• Mark Shackleton, MBBS, PhD, FRACP, director of oncology at Alfred Health, professor of oncology at Monash University, chair of Melanoma and Skin Cancer Trials Ltd, and co-director of the Monash Partners Comprehensive Cancer Consortium in Melbourne, Australia
• Daniel Heng, MD, MPH, FRCPC, clinical professor of medicine at the University of Calgary and head of medical oncology at the Arthur J.E. Child Comprehensive Cancer Centre in Calgary, Alberta, Canada

INTerpath-001: Phase 3 Study of the mRNA-Based Individualized Neoantigen Therapy Intismeran Autogene Plus Pembrolizumab vs Pembrolizumab Alone for Adjuvant Treatment of Resected Stage IIB-IV Melanoma

Findings showed from the phase 3 INTerpath-001 trial, showed that at a median follow-up of 24.6 months, inintismeran autogene plus pembrolizumab (n = 757) improved recurrence-free survival (RFS) vs placebo plus pembrolizumab (n = 380) in patients with resected stage IIB to IV melanoma, reducing the risk of recurrence or death by 42% (HR, 0.58; 95% CI, 0.45-0.75; P < .001).¹ The 24-month RFS rates were 82.2% (95% CI, 79.3%-84.8%) vs 70.0% (95% CI, 65.0%-74.5%), respectively. Distant metastasis-free survival also favored the combination (HR, 0.62; 95% CI, 0.45-0.85; P = .002), with 24-month rates of 88.5% vs 80.2%.

Overall survival data were immature (HR, 0.77; 95% CI, 0.45-1.31; P = .33). Grade 3 or higher adverse effects occurred in 23.6% of patients who received the combination vs 20.3% of those who received pembrolizumab alone.

Shackleton: The main one that’s on my mind, of course, because I also work in cutaneous melanoma, is the data from the adjuvant mRNA vaccine [study of] pembrolizumab plus or minus a bespoke neoantigen-based mRNA vaccine. That’s an important concept that has been around for a long time. Thirty-, 40-plus years ago, people were removing melanomas and mushing them up and extracting proteins and then reinjecting them into patients to try and induce immune responses. The concept has been around for a long time, and I guess this is the real modern, cutting-edge technology now that’s being applied to see if that concept works. As a proof of concept, it’s incredibly important and encourages those of us working at that cutting-edge interface to try and improve the effectiveness of immunotherapies. It gives us tremendous impetus to go down that highly personalized, neoantigen-based approach.

Schadendorf: We were all excited about seeing that a patient-specific neoantigen vaccine added to pembrolizumab, made such a big difference in RFSl and DMFS benefit. I believe that these mRNA vaccines will be a new step in oncology treatment over the next decade.

Heng: The most exciting was Georgina Long, MD’s, presentation at the ESMO plenary, the INTerpath-001 study, looking at the Moderna vaccine [intismeran autogene] plus pembrolizumab. That’s in melanoma: can we translate that to renal cell carcinoma?

Positioning Adjuvant Personalized Vaccination in the Neoadjuvant Era

INTerpath-001 evaluated intismeran autogene in the adjuvant setting, whereas neoadjuvant immunotherapy has increasingly shaped the management of resectable high-risk melanoma.

Shackleton: An interesting question, though, [arises] in a complex dynamic around the adjuvant melanoma space, which has been particularly influenced by the neoadjuvant therapy era. It’s pretty clear from the data published so far in previous studies that neoadjuvant immunotherapy for [patients with melanoma] is clearly better than no neoadjuvant therapy and adjuvant therapy only. Where this adjuvant approach of adding in personalized vaccination will fit in the neoadjuvant paradigm is the next interesting question.

References

1. 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: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA1.
2. Adjuvant intismeran autogene plus pembrolizumab improves RFS and DMFS in melanoma. OncLive. October 24, 2026. Accessed November 4, 2026. https://www.onclive.com/view/adjuvant-intismeran-autogene-plus-pembrolizumab-improves-rfs-and-dmfs-in-melanoma