Replimune Reveals IGNYTE Trial Data of RP1 with Nivolumab in Anti-PD1 Resistant Melanoma at ESMO 2024

Replimune Group, Inc., a clinical-stage biotechnology company specializing in novel oncolytic immunotherapies, has recently presented data from the primary analysis of the IGNYTE clinical trial. This study investigated the efficacy of RP1 combined with nivolumab in patients with advanced-stage melanoma who had previously failed anti-PD1 therapy. The data were presented by Dr. Caroline Robert from Gustave Roussy during the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona.

The IGNYTE trial included 140 patients who had shown disease progression despite at least eight weeks of anti-PD1-based treatment, with or without anti-CTLA-4. The study’s primary endpoint was the overall response rate (ORR), assessed by modified RECIST (mRECIST) 1.1 criteria. A secondary sensitivity analysis was also performed using RECIST 1.1 criteria as requested by the FDA. The trial results revealed a 33.6% ORR by mRECIST and 32.9% by RECIST 1.1. The complete response rate was 15% by mRECIST.

Among patients who had previously received both anti-PD1 and anti-CTLA-4 therapies, the ORR was 27.7%. For those exhibiting primary resistance to anti-PD1, the ORR was 35.9%. Notably, the responses were consistent across injected and non-injected lesions, including visceral lesions. The median duration of response from the initiation of treatment was 27.6 months, with 85% of responses persisting for more than a year.

The data also highlighted promising survival rates. Although median overall survival has yet to be achieved, the one-year, two-year, and three-year survival rates were 75.3%, 63.3%, and 54.8%, respectively.

Dr. Kostas Xynos, Chief Medical Officer of Replimune, expressed optimism about the findings, emphasizing the potential of RP1 plus nivolumab as a new treatment option for patients with anti-PD1 failed melanoma. The company plans to submit a Biologics License Application (BLA) for RP1 in the second half of 2024, marking a significant milestone.

In terms of safety, the combination of RP1 and nivolumab was generally well-tolerated. Most adverse events were Grade 1 or 2, including fatigue, chills, and fever. Grade 3-4 events were less common, affecting 12.8% of patients, and included conditions like increased lipase levels and myocarditis. Importantly, no Grade 5 adverse events were reported.

RP1, Replimune’s lead product candidate, is engineered from a proprietary strain of the herpes simplex virus. It is designed to maximize tumor cell killing and enhance the immune system’s response to cancer. RP1 incorporates a fusogenic protein (GALV-GP R-) and GM-CSF, which are intended to increase its potency and immunogenicity.

Founded in 2015 and headquartered in Woburn, MA, Replimune aims to revolutionize cancer treatment through its RPx platform, which combines localized and systemic anti-tumor activity. This platform is designed to be effective both as a standalone treatment and in combination with other cancer therapies.

The IGNYTE trial results are expected to support the BLA submission for RP1, which could provide a much-needed treatment option for patients with limited alternatives. Replimune remains dedicated to advancing its clinical programs and exploring the full therapeutic potential of its oncolytic immunotherapy platform.

The detailed presentation of the IGNYTE trial data is available on Replimune’s website under the Events and Presentations section.