Promising Efficacy of RP1/Nivolumab in Advanced Melanoma Treatment

The recent findings from the IGNYTE trial, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, highlight significant advancements in the treatment of advanced melanoma utilizing a combination of RP1 and nivolumab (Opdivo). This innovative therapy showcases a robust systemic antitumor response, particularly among patients who have previously failed PD-1 inhibitor treatments.

The study, led by Dr. Gino Kim In, a medical oncologist at Keck Medicine of the University of Southern California, involved a cohort of 140 patients with advanced melanoma who exhibited disease progression after anti-PD-1 therapy. The trial assessed the efficacy of RP1, a herpes simplex virus type 1-based oncolytic immunotherapy, in combination with nivolumab, a PD-1 inhibitor. According to the findings, the objective response rate (ORR) across the study population was reported at 32.9%, with notable variations depending on the injection method. Specifically, patients receiving deep or visceral injections combined with superficial injections achieved an ORR of 42.9%, compared to 29.8% for those receiving superficial injections alone.

"These data indicate that the combination of RP1 and nivolumab not only enhances efficacy but also maintains a manageable safety profile," Dr. In stated. The study revealed that pneumothorax events occurred in 5.8% of lung injections, primarily at grades 1 and 2, with most incidents resolving spontaneously without further intervention.

The IGNYTE trial's design included a dose-escalation and -expansion model, where patients initially received RP1 at a dose of 10^6 PFU/mL, followed by an increased dose of 10^7 PFU/mL alongside nivolumab at 240 mg biweekly. The primary endpoints focused on the safety and efficacy of the treatment regimen, evaluated using modified RECIST 1.1 criteria, with secondary endpoints encompassing overall survival and progression-free survival rates.

Historically, advanced melanoma has posed significant treatment challenges, especially in patients who have undergone multiple lines of therapy. The introduction of RP1 represents a shift towards utilizing oncolytic virotherapy in conjunction with immunotherapy. The FDA has recognized the potential of this treatment, granting priority review for a biologics license application in January 2025, based on the promising preliminary results from the IGNYTE trial.

In addition to the positive efficacy outcomes, safety assessments indicated that the majority of treatment-related adverse effects were mild to moderate, with fatigue and mild febrile reactions being the most common. The study's safety profile was deemed acceptable, with no severe bleeding events noted following liver injections.

The implications of these findings extend beyond immediate clinical outcomes; they suggest a new paradigm in treating resistant melanoma cases. As Dr. Kim stated, "The study’s results support deeper injections as a viable option for improving response rates in advanced melanoma patients, suggesting that localized immunotherapy can yield systemic responses."

The international oncology community is watching closely as further analyses and longer-term follow-ups will shed light on the durability of responses and overall survival benefits associated with this treatment strategy. Future research may also explore additional combinations of oncolytic therapies and immune checkpoint inhibitors, potentially broadening the scope of treatment options available for melanoma patients worldwide.

In conclusion, the RP1/nivolumab combination represents a significant advancement in the field of oncology, offering hope for improved outcomes in a patient population that has historically had limited therapeutic options. Continued investigation into this combination therapy will be essential in defining its role in the evolving landscape of melanoma treatment.