Impact of IGNYTE Trial Responses to RP1/Nivolumab in Advanced Melanoma

Sarah Weiss, MD, provided an in-depth look at the clinical activity of the oncolytic immunotherapy vusolimogene oderparepvec (RP1) in combination with nivolumab (Opdivo) for patients with advanced cutaneous melanoma.

Drawing from the registrational cohort of the phase 1/2 IGNYTE trial (NCT03767348), Weiss detailed the characteristics of the 15% of patients who achieved a complete response, many of whom represented a refractory population with primary resistance to prior anti-PD-1 therapies.¹ Despite the combination demonstrating a tolerable safety profile and a 2-year overall survival rate exceeding 60%, the treatment has faced significant regulatory hurdles.

In April 2026, the FDA issued a second complete response letter (CRL) for the RP1 and nivolumab combination.² The agency cited that the data provided from the IGNYTE trial were insufficient to establish substantial evidence of effectiveness for this patient population. Furthermore, the FDA noted that the trial was not considered a well-controlled clinical study and highlighted concerns regarding the heterogeneity of the patient population, which hindered a clear interpretation of the results.

Weiss, director of the Melanoma/Cutaneous Oncology Program, medical oncologist, and associate professor of medicine in the Division of Medical Oncology at Rutgers Cancer Institute, spoke with CancerNetwork® prior to the CRL, to discuss the findings from the trial and their implications into clinical practice.

Transcript:

With the 15% of responders, it was 21 patients, those patients, their characteristics seem to be that most of them had received prior anti-PD-1 therapy, not necessarily anti-CTLA-4. Although there were several patients who did receive anti-CTLA-4, they tended to have earlier stage disease, but there were responders who had more advanced disease, and most of them had primary resistance. It represents this refractory population who we’re not used to seeing complete responses in with second- or third-line therapies. It highlights the activity of this combination. [It] was tolerable, and it had some durability. The overall survival at 2 years was over 60% and with a tolerable therapy and some durability this could be, potentially, an option for patients who are progressing on PD-1.

References

1. In GK, Wong MKK, Sacco JJ, et al. Response analysis for injected and non-injected lesions and of the safety and efficacy of superficial and deep/visceral RP1 injection in the registrational cohort of anti–PD-1–failed melanoma patients of the IGNYTE trial. J Clin Oncol. 2025;43(suppl 16):9537. doi:10.1200/JCO.2025.43.16_suppl.9537
2. Complete response. April 10, 2026. FDA. Accessed April 15, 2026. https://tinyurl.com/ys3etmrj