Replimune Group announced primary analysis data from the IGNYTE clinical trial, revealing promising results for RP1, an oncolytic immunotherapy, when combined with nivolumab in patients with melanoma who had previously failed anti-PD1 therapy. The data, presented at the European Society for Medical Oncology (ESMO) Congress 2024, highlights the potential of this combination as a new treatment option for a challenging patient population. The study included 140 patients who received RP1 plus nivolumab after confirmed progression on anti-PD1 based therapy.
Key Efficacy Findings
The IGNYTE trial demonstrated clinically meaningful activity across various subgroups, including those with prior anti-CTLA-4 exposure and primary resistance to anti-PD1. The overall response rate (ORR) was 33.6% by modified RECIST (mRECIST) 1.1 criteria and 32.9% by RECIST 1.1 criteria. The complete response rate was 15% by mRECIST.
Notably, in patients who had prior anti-PD1 and anti-CTLA-4 treatment, the ORR was 27.7%, and for those with primary resistance to anti-PD1, the ORR was 35.9% by mRECIST. The median duration of response from treatment initiation was 27.6 months. At the time of the analysis, 85% of responses were ongoing more than a year from starting treatment.
Survival Rates
While median overall survival has not been reached, the one-, two-, and three-year survival rates were 75.3%, 63.3%, and 54.8%, respectively. These survival rates are particularly encouraging given the advanced stage and treatment-refractory nature of the patient population.
Tolerability and Safety
RP1 combined with nivolumab continues to be well-tolerated. Treatment-related adverse events were predominantly Grade 1-2 constitutional type events (> 5% of patients), including fatigue, chills, pyrexia, nausea, influenza-like illness, injection-site pain, diarrhea, vomiting, headache, pruritis, asthenia, arthralgia, myalgia, decreased appetite, and rash. Grade 3-4 events occurred in 12.8% of patients, with Grade 4 events including lipase increased, cytokine release syndrome, myocarditis, hepatic cytolysis and splenic rupture. There were no Grade 5 events.
Mechanism of Action and Systemic Response
An interesting observation from the trial was that injected and non-injected lesions responded with similar frequency, depth, duration, and kinetics. This suggests that RP1's mechanism of action involves generating a systemic anti-tumor immune response, which is crucial for addressing metastatic disease.
Regulatory and Financial Implications
Kostas Xynos, MD, PhD, MBA, Chief Medical Officer of Replimune, stated, "These positive data will form the basis of our upcoming BLA submission for RP1 in anti-PD1 failed melanoma in the 2H 2024." This regulatory milestone could provide a significant revenue opportunity for Replimune, addressing a market with limited treatment options.
Expert Commentary
Caroline Robert, M.D., Ph.D. of Gustave Roussy, presented the data at ESMO 2024, highlighting the clinically meaningful activity observed across all subgroups. The durable responses and manageable safety profile position RP1 plus nivolumab as a potential advancement in treating anti-PD1 refractory melanoma, addressing an unmet medical need.
