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.
