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Dr Pavlick on the Mechanisms of Action of RP1 in Cutaneous Melanoma

Anna C. Pavlick, DO, discusses the mechanism of action of vusolimogene oderparepvec in patients with anti–PD-1–failed cutaneous melanoma.

Anna C. Pavlick, DO, professor of medicine, the Division of Hematology and Medical Oncology, Weill Cornell Medicine, founding director, the Cutaneous Oncology Program, Weill Cornell Medicine and New York-Presbyterian, discusses the mechanism of action of vusolimogene oderparepvec (RP1) in patients with anti–PD-1–failed cutaneous melanoma.

RP1 could be considered the next generation of talimogene laherparepvec (T-VEC), which was a first-in-class oncolytic immunotherapy previously approved for the treatment of patients with advanced melanoma, Pavlick begins. Similarly, RP1 is a proprietary new strain of herpes simplex virus with mechanisms that tend to differ from T-VEC, Pavlick adds. In RP1, the neurovirulence gene is deleted, allowing the vaccine to be distributed and deposited within the tumor cells while sparing normal, healthy cells, Pavlick adds.

Moreover, RP1 is encoded with granulocyte-macrophage colony-stimulating factor (GM-CSF), which can lead to a triggering of an immune response, Pavlick continues. Additionally, the oncolytic virus is also encoded with GAL-GP, which cell-to-cell cytotoxicity. Therefore, if a cell dies, it is going to kill its neighboring cell, Pavlick notes.

The phase 2 IGNYTE trial (NCT03767348) is examining RP1 in combination with nivolumab (Opdivo) in 3 tumor-specific cohorts, including 1 featuring patients with anti–PD-1–failed cutaneous melanoma.

Although the IGNYTE trial began as a phase 2 study, investigators added an expansion arm for patients with cutaneous melanoma, aiming to enroll 125 patients in this patient subgroup who have progressed on anti–PD-1 therapy. Data from the first 75 patients showed that the overall response rate was 36%, including a complete response rate of 20%. Additionally, these responses are consistent with initial data with RP1.

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