Genetically Modified Herpesvirus Shows Promise in Melanoma Treatment

A recent clinical trial has revealed that a genetically modified version of the herpes simplex virus type 1 (HSV-1), combined with the immunotherapy drug nivolumab, has shown significant potential in treating late-stage melanoma. This innovative approach targets patients whose tumors have become resistant to traditional therapies, marking a promising advancement in cancer treatment. According to Dr. Gino In, an oncologist at Keck Medicine of USC and coauthor of the study published in the Journal of Clinical Oncology on July 8, 2025, the combination therapy resulted in tumor shrinkage or elimination in one-third of participants after they had exhausted standard treatment options.

Melanoma, a severe form of skin cancer, accounts for a disproportionate number of skin cancer deaths despite being less common than other types of skin cancer. The American Cancer Society reported that melanoma is responsible for about 1 in 100 cases of skin cancer, yet over the past decade, death rates have improved due to advancements in immunotherapy (American Cancer Society, January 16, 2025). However, the effectiveness of these treatments varies, and many patients face limited options when standard therapies fail.

The RP1 therapy, as it is known, has a unique mechanism of action. Researchers engineered the virus to eliminate its disease-causing attributes while enhancing its cancer-fighting capabilities. This modification involved removing harmful genes from the virus, allowing it to infect and attack cancer cells more effectively, as explained by Dr. In. The treatment was administered through injections directly into the tumor sites, which included various locations such as skin, lymph nodes, and internal organs. Remarkably, not only did the injected tumors shrink in one-third of patients, but tumors that were not directly treated also exhibited significant responses, suggesting a systemic effect of the therapy.

Dr. Shailender Bhatia, Director of the Melanoma and Renal Cancer Team at Fred Hutch Cancer Center, noted that the results were particularly exciting for late-stage melanoma patients. He added that the potential applicability of RP1 may extend to other cancers, as the findings suggest a broader capability to combat tumors beyond those directly injected.

The clinical trial enrolled 140 participants with advanced melanoma, all of whom had tumors that continued to progress despite standard immunotherapy treatments. Participants received RP1 injections every two weeks, up to eight doses, alongside nivolumab, an established immune checkpoint inhibitor. Dr. Amanda Kirane, Director of Cutaneous Surgical Oncology at Stanford Cancer Center, commented on the implications of the findings, highlighting the treatment's potential for tumors in hard-to-reach areas, which could significantly enhance treatment options for patients with metastasized cancers.

The safety profile of RP1 appears favorable, with most side effects reported as mild and flu-like. Dr. In emphasized that the one-third response rate is competitive when compared to other therapies, such as tumor-infiltrating lymphocyte (TIL) therapy, which requires hospitalization due to severe side effects, or the combination of nivolumab with relatlimab, which has lower efficacy rates.

As the researchers prepare for a Phase 3 trial, IGNYTE-3, to validate their findings in a larger cohort, the treatment is under priority review by the U.S. Food and Drug Administration (FDA). A decision on its potential accelerated approval is expected by July 2025, according to Dr. In, who expressed optimism that this breakthrough could significantly alter the treatment landscape for melanoma patients.

This development underscores the transformative potential of viral therapies in oncology, representing a shift towards harnessing the body’s immune system to combat cancer effectively. As research progresses, patients with late-stage melanoma are encouraged to explore clinical trial options, further highlighting the importance of continued innovation in cancer treatment.