Genetically Modified Herpes Virus Shows Promise in Advanced Melanoma Treatment

A recent clinical study has highlighted the potential of a genetically modified herpes simplex virus type 1 (HSV-1), known as RP1, as an innovative treatment for advanced melanoma, a deadly form of skin cancer. Results from the phase 1-2 IGNYTE clinical trial, published in the Journal of Clinical Oncology, indicate that RP1, when combined with the immunotherapy nivolumab, led to significant tumor shrinkage in approximately one-third of participants who had previously unresponsive melanoma. The trial involved 140 patients from various global sites, including Keck Medicine of USC, and was presented at the 2025 American Society of Clinical Oncology annual meeting.

Melanoma ranks as the fifth most prevalent cancer among adults, with nearly half of advanced cases resistant to existing immunotherapies. Dr. Gino Kim In, a medical oncologist at Keck Medicine and principal investigator in the study, emphasized the urgency of developing effective treatments for this patient population. "The survival rate for untreatable advanced melanoma is alarmingly low, often measured in mere years. This novel therapy offers a glimmer of hope for individuals with limited options," stated Dr. In during a recent interview.

The RP1 virus operates as an oncolytic virus, a class of treatment designed to selectively target and destroy cancer cells while simultaneously stimulating an immune response throughout the body. Unlike traditional HSV-1, the genetically modified RP1 does not cause herpes. Instead, it replicates within tumors and prompts the immune system to attack both treated and untreated cancer cells. The trial also demonstrated that tumors shrank in patients who were not directly injected with the virus, suggesting RP1's systemic efficacy.

The study's findings revealed that tumors in about 33% of the patients shrank by at least 30%, with complete tumor disappearance observed in nearly 17% of participants. Furthermore, the combination therapy was well-tolerated, with a favorable safety profile. As Dr. In noted, the treatment regimen involved administering RP1 and nivolumab biweekly for up to eight cycles, followed by continued nivolumab administration for patients who responded favorably.

The U.S. Food and Drug Administration (FDA) granted priority review for RP1 in combination with nivolumab earlier this year, marking a significant step toward potential approval for patients with advanced melanoma unresponsive to prior treatments. The promising outcomes of the phase 1-2 trial have led researchers to initiate a phase 3 trial, known as IGNYTE-3, which aims to validate these results across a larger, more diverse patient population exceeding 400 participants.

This development is particularly noteworthy in light of the increasing incidence of melanoma, driven by factors such as increased sun exposure and tanning bed usage. The American Cancer Society projects that over 100,000 new melanoma cases will be diagnosed in the United States in 2025 alone.

Experts in oncology are optimistic about the implications of oncolytic virus therapy in the broader landscape of cancer treatment. Dr. Phillip M. Cheng, a diagnostic radiologist involved in the study, remarked, "The use of genetically modified viruses like RP1 represents a groundbreaking shift in how we conceptualize cancer treatment. It opens the door for innovative therapies that harness the body's immune system in unprecedented ways."

As the phase 3 trial progresses, the medical community remains hopeful that RP1 could become a mainstream treatment option for patients battling advanced melanoma and potentially other cancer types in the future. The ongoing research underscores the importance of continued investment in novel therapeutic approaches, particularly in an era where treatment resistance poses significant challenges in oncology.