Replimune Group Inc. presented late-breaking data from the IGNYTE clinical trial at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2024), showcasing the potential of RP1 in combination with nivolumab for patients with melanoma who have progressed on anti-PD-1 therapy. The data demonstrated promising anti-tumor activity and a manageable safety profile, offering a potential new treatment option for this challenging patient population.
IGNYTE Trial Results
The IGNYTE trial included 140 patients with anti-PD-1 failed melanoma who received RP1 plus nivolumab after confirmed progression on anti-PD-1 based therapy for at least 8 weeks, with or without anti-CTLA-4. The primary analysis, conducted after a median follow-up of 15.4 months, revealed a 33.6% overall response rate (ORR) by modified RECIST (mRECIST) v1.1 criteria, the trial's primary endpoint. An additional analysis requested by the FDA showed a 32.9% ORR by RECIST v1.1 criteria. The complete response (CR) rate by mRECIST v1.1 was 15%.
Notably, the ORR was 27.7% in patients who had prior anti-PD1 and anti-CTLA-4 treatment and 35.9% in those with primary resistance to anti-PD1, suggesting the combination's efficacy across different subgroups. The median duration of response from response initiation was 21.6 months, indicating durable benefit.
Kostas Xynos, MD, PhD, MBA, Chief Medical Officer of Replimune, stated, "We believe that the systemic activity of RP1 and nivolumab is in particular demonstrated by the similar level of responses seen in both injected and non-injected lesions, including hard to treat visceral lesions, and by the durability of the responses seen."
Systemic Activity and Biomarker Analysis
The trial data indicated that RP1 plus nivolumab induced deep responses in both injected and non-injected lesions, including those in visceral organs distant from the injection site. Most injected and non-injected lesions (85%) in responders had a 30% or greater reduction in size, highlighting the systemic activity of the combination.
Initial biomarker data revealed an increase in the expression of genes associated with CD8+ T cells and inflammatory cytokines, as shown by tumor inflammation signature (TIS) and nano string analysis. Immunohistochemistry (IHC) images suggested that RP1 plus nivolumab may stimulate tumors to a more immune-inflamed state, potentially reversing mechanisms of resistance to anti-PD-1 therapy.
Survival Rates and Tolerability
Median overall survival for the trial has not been reached. However, the one-, two-, and three-year survival rates were 75.3%, 63.3%, and 54.8%, respectively. The 12-month progression-free survival (PFS) was 32.8%, and the median PFS was 3.7 months.
The combination of RP1 and nivolumab was generally well-tolerated. Treatment-related adverse events were predominantly Grade 1-2 constitutional type events, such as fatigue, chills, and pyrexia. Grade 3-4 events occurred in 12.8% of patients, with no Grade 5 events reported.
Ongoing Phase 3 Trial
The IGNYTE-3 confirmatory phase 3 trial, evaluating RP1 plus nivolumab versus physician’s choice in patients with advanced melanoma who have progressed on anti-PD1 and anti-CTLA-4 or who are not candidates for anti-CTLA-4 therapy, is currently recruiting.
