Replimune Group, Inc. presented late-breaking data from its IGNYTE clinical trial at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting, showcasing the potential of RP1 in combination with nivolumab for patients with advanced melanoma who have progressed on anti-PD-1 therapy. The data demonstrated significant anti-tumor activity and durable responses, suggesting a promising new treatment option for this challenging patient population.
IGNYTE Trial Results
The IGNYTE trial enrolled 140 patients with anti-PD-1 failed melanoma who received RP1 plus nivolumab after confirmed progression on anti-PD-1 based therapy. The primary analysis, conducted after a median follow-up of 15.4 months, revealed an overall response rate (ORR) of 33.6% by modified RECIST (mRECIST) v1.1 criteria. The complete response (CR) rate 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.
Kostas Xynos, MD, PhD, MBA, Chief Medical Officer of Replimune, stated, "The initial biomarker analyses included in the SITC presentation which demonstrate increases in tumor CD8+ T cell infiltration and PD-L1 expression along with the induction of an immune inflammatory gene signature after treatment, 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."
Durability of Response and Survival Rates
The median duration of response from response initiation was 21.6 months, indicating a sustained benefit for responding patients. The study also reported encouraging survival rates, with one-, two-, and three-year survival rates of 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.
Mechanism of Action and Biomarker Analysis
Biomarker data from the IGNYTE trial showed an increase in the expression of genes associated with CD8+ T cells and inflammatory cytokines, suggesting that RP1 plus nivolumab can generate a potent anti-tumor immune response. Immunohistochemistry (IHC) images further demonstrated that the combination therapy may stimulate tumors to a more immune-inflamed state, potentially reversing resistance to anti-PD-1 therapy.
Tolerability
RP1 combined with 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 and included lipase increased, cytokine release syndrome, myocarditis, hepatic cytolysis, and splenic rupture. There were no Grade 5 events reported.
Ongoing Phase 3 Trial
The IGNYTE-3 confirmatory phase 3 trial is currently recruiting 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 evaluate the efficacy and safety of RP1 plus nivolumab compared to physician's choice of therapy.
