Replimune Presents Data on RP1 and Nivolumab for Anti-PD1 Failed Melanoma at SITC 2024

Replimune Group, Inc., a clinical-stage biotech company focused on innovative oncolytic immunotherapies, presented significant findings from the IGNYTE clinical trial at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) 2024 in Houston, Texas. The trial's data, including initial biomarker analyses, were showcased in a late-breaking oral session. Additionally, results from the ARTACUS clinical trial, which appraises RP1 monotherapy in solid organ transplant patients with advanced cutaneous malignancies, were presented in an encore poster.

Kostas Xynos, MD, PhD, MBA, Chief Medical Officer at Replimune, emphasized the promising initial biomarker analyses from the SITC presentation. These analyses demonstrated increased tumor CD8+ T cell infiltration and PD-L1 expression, along with the induction of an immune-inflammatory gene signature post-treatment. This data supports the mechanism of RP1 in combination with nivolumab, showing its potential to induce a systemic response even after prior anti-PD1 therapy progression. Xynos highlighted that the systemic activity of RP1 and nivolumab is evident from the similar response levels in both injected and non-injected lesions, including difficult-to-treat visceral lesions, and the durability of these responses.

The IGNYTE trial data involved 140 patients with anti-PD-1 failed melanoma who received RP1 plus nivolumab after confirming progression while on anti-PD-1 based therapy for at least eight weeks, with or without anti-CTLA-4. The primary analysis, conducted by blinded independent central review, occurred after a 12-month follow-up period for all patients, with a median follow-up of 15.4 months.

Key findings from the IGNYTE trial included:
- A confirmed response rate of 33.6% by modified RECIST (mRECIST) v1.1 criteria, and 32.9% by RECIST v1.1 criteria.
- The complete response (CR) rate by mRECIST v1.1 was 15%.
- Patients with prior anti-PD1 and anti-CTLA-4 treatments showed an ORR of 27.7%, while those with primary resistance to anti-PD1 exhibited an ORR of 35.9%.
- The median duration of response was 21.6 months.
- 85% of injected and non-injected lesions in responders saw a reduction in size by 30% or more.
- RP1 plus nivolumab induced deep responses in non-injected visceral lesions, including those far from the injection site.
- Median overall survival has not been reached, but 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.

Initial biomarker data from the SITC presentation further revealed:
- Increases in gene expression associated with CD8+ T cells and inflammatory cytokines.
- Tumor inflammation signature (TIS) and nano string analysis showed an increase in expression of genes linked to CD8+ T cells and inflammatory cytokines, indicating the potential of RP1 plus nivolumab to generate a potent anti-tumor immune response.
- Immunohistochemistry (IHC) images suggested that RP1 plus nivolumab could stimulate tumors to a more immune inflamed state, potentially reversing resistance mechanisms to anti-PD1 therapy.

RP1 combined with nivolumab has continued to show an acceptable safety profile, with most treatment-related adverse events being Grade 1-2, such as fatigue, chills, fever, nausea, and injection-site pain. Only a small percentage (12.8%) of patients experienced Grade 3-4 events, with no Grade 5 events reported.

The IGNYTE-3 confirmatory phase 3 trial is currently recruiting and aims to evaluate RP1 plus nivolumab against physicians' choice in patients with advanced melanoma who have progressed on anti-PD1 and anti-CTLA-4 or are not candidates for anti-CTLA-4 therapy.

Replimune Group, Inc., founded in 2015 and headquartered in Woburn, MA, focuses on transforming cancer treatment through novel oncolytic immunotherapies. The company's RPx platform, based on a potent HSV-1 backbone, is designed to maximize immunogenic cell death and induce a robust systemic anti-tumor immune response. This platform is versatile, potentially working alone or in combination with other cancer treatments.