When combined with nivolumab, RP1 (vusolimogene oderparepvec), a genetically engineered herpes simplex virus type 1–based oncolytic immunotherapy, induced deep and durable systemic responses in patients with advanced melanoma who have failed to respond to prior anti–PD-1 therapy, according to findings from the phase I/II IGNYTE trial published in the Journal of Clinical Oncology.
“These findings are very encouraging because melanoma is the fifth most common cancer for adults, and about half of all advanced melanoma cases cannot be managed with currently available immunotherapy treatments,” said IGNYTE investigator Gino Kim In, MD, a medical oncologist with Keck Medicine. “The survival rate of untreatable advanced melanoma is only a few years, so this new therapy offers hope to patients who may have run out of options to fight the cancer.”
Background and Study Methods
The U.S. Food and Drug Administration granted Priority Review designation to the combination of RP1 and nivolumab for patients with advanced melanoma who have not responded to prior immunotherapy in January 2025.
The phase I/II IGNYTE trial enrolled 140 patients with advanced melanoma who had confirmed disease progression on anti–PD-1 therapy as their most recent treatment. RP1 was administered intratumorally every 2 weeks for up to eight doses at up to 10 mL/dose, though additional doses were allowed, with up to 2 years of nivolumab.
Of these patients, just under half had stage IVM1B/C/D disease, 66% had primary anti–PD-1 resistance, 56% had PD-L1–negative disease, and 46% received prior anti–CTLA-4 therapy in addition to anti–PD-1 (either in combination or sequentially).
Key Study Findings
The confirmed objective response rate was 32.9%, including complete responses in 15%. The median duration of response was 33.7 months. The 1-year overall survival rate was 75.3%, and the 2-year rate was 63.3%.
Responses were seen in both injected and noninjected lesions. “This result suggests that RP1 is effective in targeting cancer throughout the entire body and not just the injected tumor, which expands the potential effectiveness of the drug because some tumors may be more difficult or impossible to reach,” said Dr. In, who is also a member of USC Norris Comprehensive Cancer Center.
Treatment-related adverse events of grade 1 or 2 were 77.1%, grade 3 rates were 9.3%, grade 4 rates were 3.6%, and there were no observed grade 5 events. The safety profile was considered favorable by the investigators.
Biomarker analysis showed broad immune activation that was associated with responses.
“I believe that oncolytic viruses will open up an important new approach to fighting cancer in some patients in the near future,” concluded Dr. In.
Going forward, a phase III study for the combination, called IGNYTE-3, has been launched to confirm these study findings.
Disclosure: The study was sponsored by Replimune. For full disclosures of the study authors, visit ascopubs.org.
