Herpes virus for the treatment of melanoma

A genetically modified herpes virus called RP1(vusolimogene oderparepvec) could soon become the second  cancer-killing virus to be approved in the United States. RP1is a selectively replication-competent herpes simplex virus type 1–based oncolytic immunotherapy.

At the 2025 ASCO Annual Meeting, Gino Kim In, MD, 1 a medical oncologist, and associate professor of clinical medicine at Keck School of Medicine of the University of Southern California, discussed the safety and efficacy of superficial and deep or visceral RP1 injections in a registrational cohort of patients from the phase 2 IGNYTE trial (NCT03767348) with melanoma who progressed on anti–PD-1 inhibitors.

This open-label, dose-escalation and expansion study evaluated RP1 plus nivolumab (Opdivo) for patients with advanced melanoma who experienced disease progression on prior anti–PD-1 therapy, had measurable disease, and adequate organ function, an ECOG performance status of 0 or 1, and no prior exposure to oncolytic therapy.

RP1 was injected into superficial and/or deep/visceral lesions, in which superficial tumors were defined as those that could be visualized and accessed via standard needle and syringe sizes. Deep/visceral tumors could not be directly observed and required imaging guidance prior to injection. Both superficial and deep/visceral lesions could receive the injections on the same day, with the volume dependent on lesion size.

Meaningful systemic responses were observed irrespective of the injection status of individual lesions or their anatomical location, he continued. These results indicate that the overall response was driven by the effect on both injected and non-injected lesions. Furthermore, the safety profile of deep or visceral RP1 injections was consistent with that of superficial injections, and efficacy remained similar across these groups, Dr. In noted.

RP1 + nivolumab was well tolerated. Deep injections into lung and liver were generally safe, with few organ-specific AEs and no bleeding events after liver injection. Biomarker assessments revealed increased CD8+ infiltration and PDL1 upregulation in many patients.

Overall, the study findings support the potential systemic activity of RP1 combined with nivolumab in patients with melanoma who have progressed on prior anti-PD-1 therapy. This combination provided deep and durable systemic responses, even in patients with poor prognostic factors, and demonstrated a favorable safety profile.

A confirmatory phase 3 trial, IGNYTE-3 (NCT06264180), comparing RP1 + nivolumab vs physician’s choice is now under way.

(1) J Clin Oncol. 2025;43(suppl 16):9537.