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 treating melanoma patients who have failed prior anti-PD-1 therapy. The data highlight significant anti-tumor activity and durable responses across various patient subgroups.
IGNYTE Trial Results
The IGNYTE trial included 140 patients with anti-PD-1 failed melanoma, all of whom had experienced confirmed progression after at least 8 weeks of anti-PD-1 based therapy, with or without anti-CTLA-4. The primary analysis, conducted after a minimum 12-month follow-up, revealed promising outcomes.
The overall response rate (ORR) was 33.6% per modified RECIST (mRECIST) v1.1 criteria, the trial's primary endpoint, and 32.9% per RECIST v1.1 criteria, an additional analysis requested by the FDA. The complete response (CR) rate by mRECIST v1.1 stood at 15%. Notably, patients who had previously received both anti-PD1 and anti-CTLA-4 therapy showed an ORR of 27.7%, while those with primary resistance to anti-PD1 had an ORR of 35.9% by mRECIST v1.1.
"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," said Kostas Xynos, MD, PhD, MBA, Chief Medical Officer of Replimune.
The median duration of response from response initiation was 21.6 months. Impressively, 85% of both injected and non-injected lesions in responders experienced a 30% or greater reduction in size. The therapy also induced deep responses in non-injected lesions within visceral organs, even those distant from the injection site.
Median overall survival (OS) has not yet been reached, but 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%, with a median PFS of 3.7 months.
Biomarker Insights
Initial biomarker data indicated an increase in the expression of genes associated with CD8+ T cells and inflammatory cytokines, as revealed by tumor inflammation signature (TIS) and nano string analysis. Immunohistochemistry (IHC) images suggest that RP1 plus nivolumab may stimulate tumors to a more immune-inflamed state, potentially reversing resistance mechanisms to anti-PD1 therapy.
Safety Profile
RP1 combined with nivolumab continues to demonstrate a favorable safety profile. Treatment-related adverse events were mainly Grade 1-2 constitutional events, including fatigue, chills, pyrexia, and nausea. Grade 3-4 events occurred in 12.8% of patients, with single instances of lipase increase, cytokine release syndrome, myocarditis, hepatic cytolysis, and splenic rupture. No Grade 5 events were reported.
Ongoing and Future Studies
The IGNYTE-3 confirmatory phase 3 trial, which is evaluating RP1 plus nivolumab versus physician’s choice in advanced melanoma patients who have progressed on anti-PD1 and anti-CTLA-4 or are ineligible for anti-CTLA-4 therapy, is currently enrolling participants.
