Replimune Group, Inc. announced compelling primary analysis data from its IGNYTE clinical trial, revealing that RP1, when combined with nivolumab, achieved a 33.6% overall response rate (ORR) in melanoma patients who had previously failed anti-PD1 therapy. The data, presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2024), highlights the potential of this combination to address a critical unmet need in patients with advanced melanoma. The study included 140 patients with a median follow-up of 15.4 months.
Efficacy and Durability
The IGNYTE trial demonstrated not only a significant ORR but also a 15% complete response (CR) rate by modified RECIST (mRECIST) v1.1 criteria. The median duration of response was 21.6 months, showcasing the durability of the treatment effect. Furthermore, the one-, two-, and three-year survival rates were 75.3%, 63.3%, and 54.8%, respectively, underscoring the potential for long-term survival benefits.
Biomarker Analysis
Initial biomarker analyses revealed an increase in tumor CD8+ T cell infiltration and PD-L1 expression following treatment. According to Kostas Xynos, MD, PhD, MBA, Chief Medical Officer of Replimune, these findings "further support the intended mechanism of RP1 in combination with nivolumab, including its ability to induce a systemic response after progression on prior anti-PD1 therapy."
Systemic Activity
An impressive 85% of both injected and non-injected lesions in responders experienced a 30% or greater reduction in size. This systemic activity, including responses in visceral organs distant from the injection site, suggests a broad anti-tumor effect.
Safety Profile
The combination of RP1 and nivolumab was generally well-tolerated, with most treatment-related adverse events being Grade 1-2. Grade 3-4 events occurred in 12.8% of patients and included increased lipase, cytokine release syndrome, myocarditis, hepatic cytolysis, and splenic rupture. There were no Grade 5 events reported.
Ongoing Phase 3 Trial
Replimune is currently recruiting for the IGNYTE-3 confirmatory phase 3 trial, which is evaluating RP1 plus nivolumab versus physician’s choice in patients with advanced melanoma who have progressed on anti-PD1 and anti-CTLA-4 therapy or who are not candidates for anti-CTLA-4 therapy. This trial aims to further validate the efficacy and safety of this combination therapy.
Market Implications
The positive data from the IGNYTE trial could significantly strengthen Replimune's position in the melanoma therapeutics market. With a substantial portion of patients responding to the therapy and demonstrating durable responses, RP1 plus nivolumab holds promise as a valuable treatment option for a difficult-to-treat patient population.
