No New Safety Signals Seen With V940 Plus Pembrolizumab in Melanoma

Matteo S. Carlino, MD, PhD, FRACP, a medical oncologist at Westmead and Blacktown Hospitals, a faculty member at Melanoma Institute Australia, and a clinical senior lecturer at The University of Sydney in Australia, addressed the safety profile of intismeran autogene (V940) added to pembrolizumab (Keytruda) in patients with resected melanoma. A recent press release on the phase 3 INTerpath-001 trial (NCT05933577) noted no new safety signals.¹

Carlino explained why that finding is notable; combining immunotherapies typically raises the rate of immune-related adverse events, as has been observed when checkpoint inhibitor combinations are used together. He described what was instead observed when V940 was added to pembrolizumab in the randomized phase 2b KEYNOTE-942 study (NCT03897881) and outlined the distinct, generally mild toxicities associated with the mRNA vaccine component itself, drawing a comparison to adverse effects patients may already recognize from other mRNA vaccines.²

Transcript:

CancerNetwork: There were no new safety signals observed. For clinicians treating real-world patients, how does the addition of an intramuscular mRNA neoantigen vaccine impact the incidence or severity of immune-related adverse events compared with single-agent pembrolizumab?

Carlino: I thought that was one of the exciting results from the phase 2 study. Typically, when we combine drugs, we get an incremental increase in toxicity, and for immunotherapy, the worry is that we see an increased rate of immune-related adverse events. We see that when we add ipilimumab [Yervoy] to nivolumab [Opdivo] or Relatlimab-rmbw [Opdulag] to nivolumab. In the randomized phase 2 study, we saw no change in the rate of immune-related adverse events for the toxicities that we know are associated with pembrolizumab and similar drugs. We did see the [adverse] effects typically associated with mRNA-based vaccines, and these were relatively minor: arm pain at the site of injection, occasional fevers, and rigors very similar to what patients would typically remember if they’ve had an mRNA vaccine for other indications.

References

1. Merck and Moderna announce phase 3 INTerpath-001 trial of intismeran autogene plus KEYTRUDA® met endpoints of recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with completely resected stage IIB-IV melanoma. News release. August 19, 2026. Accessed August 19, 2026. https://tinyurl.com/yxe3d24n
2. Carlino MS, Khattak A, Meniawy T, et al. Individualized neoantigen therapy intismeran autogene (intismeran) plus pembrolizumab (pembro) in resected melanoma: 5-year update of the KEYNOTE-942 study. J Clin Oncol. 2026;44(suppl 16):9500. doi:10.1200/JCO.2026.44.16_suppl.9500