News|Articles|October 23, 2026

Personalized mRNA Vaccine Intismeran Plus Pembro Cuts Melanoma Recurrence

Adding the mRNA-based individualized neoantigen intismeran to pembrolizumab reduced the risk of disease recurrence or death by 42% in melanoma.

Adding intismeran autogene, an mRNA-based individualized neoantigen therapy also known as a personalized cancer vaccine, to adjuvant pembrolizumab (Keytruda) significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) vs pembrolizumab alone in patients with completely resected high-risk cutaneous melanoma, according to results from the phase 3 INTerpath-001 trial scheduled to be presented at the 2026 European Society for Medical Oncology (ESMO) Congress.^1,2

At a median follow-up of 24.6 months, intismeran plus pembrolizumab reduced the risk of disease recurrence or death by 42% vs placebo plus pembrolizumab in the intention-to-treat population (HR, 0.58; 95% CI, 0.45-0.75; P < .001). The 24-month RFS rate was 82.2% (95% CI, 79.3%-84.8%) with the combination and 70.0% (95% CI, 65.0%-74.5%) with pembrolizumab alone. Median RFS was not reached in either arm.^1,2

The investigational regimen also lowered the risk of distant metastasis or death by 38% (HR, 0.62; 95% CI, 0.45-0.85; P = .002). At 24 months, DMFS rates were 88.5% (95% CI, 86.0%-90.6%) and 80.2% (95% CI, 75.6%-84.0%) in the intismeran and control arms, respectively. Median DMFS was not reached in either group.^1,2

"In the prior phase 2 trial [of this combination], we saw a clear separation of curves in favor of improved outcomes for patients who had the vaccine in addition to pembrolizumab vs pembrolizumab alone, and in the INTerpath-001 trial, what we see is a similar sustained benefit in a much larger sample size, which is very reassuring," Janice Mehnert, MD, said in an interview with Targeted Oncology. Mehnert is associate director for Clinical Research and director, melanoma and cutaneous medical oncology, Perlmutter Cancer Center of NYU Langone Health/NYU Grossman School of Medicine.

INTerpath-001 Trial Embargo Breach Before ESMO

Merck (MSD) and Moderna, the co-sponsors of the INTerpath-001 study, released these findings for intismeran plus pembrolizumab following an embargo break ahead of the 2026 ESMO Congress. The INTerpath-001 results were not scheduled to be shared until a Presidential Session taking place at the meeting on Saturday, October 24. However, a cancer news site prematurely published an article covering the embargoed data. Following the leak, the conference lifted the embargo on the INTerpath-001 abstract and the companies sent out a news release announcing the findings. The release results, along with additional findings, will still be shared during the Saturday session.

ESMO posted a statement on the embargo breach on its official congress program page:

“The embargo on LBA1, ‘INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy intismeran autogene plus pembrolizumab versus pembrolizumab alone for adjuvant treatment of resected stage IIB-IV melanoma,’ has been breached. As the data are now publicly available, ESMO has released the information contained in the abstract and has lifted the embargo on the full dataset.”³

Additional INTerpath-001 Efficacy Results

During the first 6 months on study, outcomes were comparable between arms for both RFS (HR, 0.99; 95% CI, 0.66-1.49) and DMFS (HR, 1.01; 95% CI, 0.58-1.79). Per protocol, pembrolizumab began at randomization, while intismeran or placebo was started once the individualized product became available. Beyond 6 months, following the intismeran immunization regimen, a prespecified sensitivity analysis of the primary end point showed a 58% reduction in the risk of recurrence or death (piecewise HR, 0.42; 95% CI, 0.30-0.58) and a 50% reduction in the risk of distant metastasis or death (piecewise HR, 0.50; 95% CI, 0.34-0.73) with the combination.^1,2

In a modified intention-to-treat sensitivity analysis excluding patients who did not receive at least 1 planned dose of intismeran or placebo, the combination yielded an RFS HR of 0.51 (95% CI, 0.39-0.67), a 49% risk reduction, and a DMFS HR of 0.55 (95% CI, 0.40-0.77), a 45% risk reduction. Overall, 726 of 757 patients (95.9%) in the intismeran arm and 365 of 380 (96.1%) in the placebo arm received at least 1 dose of intismeran or placebo as planned.^1,2

Benefit was generally consistent across prespecified subgroups, including patients with stage IIB to IIIB and stage IIIC to IV disease. Overall survival (OS) data are immature, but a favorable trend has been observed, and follow-up continues. The findings have been accepted for publication in The New England Journal of Medicine, and Merck and Moderna are engaging with regulators.^1,2

“The transformative INTerpath-001 results have the potential to make a foundational shift in how we treat patients with earlier-stage melanoma in the adjuvant setting,” Georgina V. Long, MBBS, PhD, the study’s principal investigator and medical director of Melanoma Institute Australia, stated in a news release.¹ “For decades, cancer treatment has largely been defined by where a tumor originates in the body. The INTerpath-001 findings support a fundamentally new and individualized approach to treating resected melanoma in the adjuvant setting, one that tailors treatment to the unique mutational signature of a patient’s tumor to enhance an anti-tumor immune response. While these results are in patients with completely resected stage IIB-IV melanoma, they provide valuable insights and will help inform our understanding of intismeran as clinical research continues into other tumor types and across settings.”

Safety Profile of Intismeran Plus Pembrolizumab

Treatment-related adverse events (TRAEs) were reported in 95.8% (723 of 755) of patients who received intismeran plus pembrolizumab and 90.0% (342 of 380) of those given pembrolizumab alone. Grade 3 to 5 TRAEs occurred in 14.2% (n = 107) and 13.4% (n = 51), respectively.¹

Grade 3 or higher adverse events (AEs) of any attribution occurred in 23.6% of the combination arm vs 20.3% of the control arm, and 6.5% vs 5.3% of patients discontinued both study drugs at the same time because of an AE. The most frequent AEs with intismeran plus pembrolizumab vs pembrolizumab alone were pyrexia (52.2% vs 8.2%), injection site pain (51.0% vs 9.5%), and fatigue (38.5% vs 29.7%). No new safety signals emerged.^1,2

INTerpath-001 Trial Design

The global, randomized, double-blind, placebo-controlled INTerpath-001 study (NCT05933577) enrolled adults with surgically resected stage IIB or IIC (pathologic or clinical) or stage III or IV cutaneous melanoma who had a tumor sample suitable for next-generation sequencing. ²

In total, 1137 patients were randomized 2:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 9 cycles plus either intramuscular intismeran 1 mg (n = 757) or placebo (n = 380) every 3 weeks for up to 9 doses. Treatment continued until recurrence, unacceptable toxicity, or up to approximately 56 weeks.^1,2

RFS, the primary end point, was defined as the time from randomization to investigator-assessed disease recurrence at any site (local, locoregional, regional, or distant) or death from any cause. Key secondary end points include DMFS, OS, safety, tolerability, and quality of life.¹

Each intismeran product is a synthetic mRNA encoding up to 34 patient-specific neoantigens identified through tumor and normal DNA sequencing.^1,2

“INTerpath-001 is the first phase 3 study to demonstrate a clinically meaningful improvement in RFS and DMFS over standard-of-care Keytruda in patients with resected melanoma, setting a new benchmark in the adjuvant setting and representing one of the most significant advances in melanoma treatment since the advent of immunotherapy,” Dean Y. Li, MD, PhD, president of Merck Research Laboratories, stated in the release.¹“These results, building on the body of evidence from the phase 2b study, strengthen our confidence in the curative potential of intismeran autogene when given in combination with Keytruda. Importantly, these data suggest that, by intervening earlier, this approach may offer a tangible opportunity to change the trajectory of a patient’s cancer.”