A 3-year landmark overall survival analysis of RP1 plus nivolumab in patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial.

Abstract

9518 Background: Advanced melanoma has a high mortality rate; however, survival for patients (pts) treated with anti–PD-1–based therapy tends to plateau at 3–4 years, suggesting that pts alive at 3 years are likely to have prolonged benefit. This highlights the need for novel therapies that offer increased survival beyond 3-4 years. RP1 (vusolimogene oderparepvec) is an HSV-1–based oncolytic immunotherapy expressing GM-CSF and a fusogenic glycoprotein (GALV-GP-R − ). In the IGNYTE trial (data cutoff [DCO]: 15OCT2024), pts with advanced melanoma that had confirmed progression on anti–PD-1 therapy who received RP1 + nivolumab (nivo) had an objective response rate by RECIST 1.1 of 33.6% (16.4% complete response); median duration of response was 24.8 months. Here, we present a 3-year survival analysis of pts treated with RP1 + nivo from IGNYTE (last pt in: 9MAR2023; DCO: 11JUN2025). Methods: Pts ≥18 years with advanced melanoma and confirmed progression while being treated for ≥8 weeks with anti–PD-1 ± anti–CTLA-4 as the last prior therapy were enrolled (NCT03767348). An initial dose of RP1 was administered intratumorally (1 × 10 6 PFU/mL), followed by up to 7 doses every 2 weeks (Q2W; 1 × 10 7 PFU/mL) in combination with intravenous nivo 240 mg Q2W/480 mg Q4W for up to 2 years; additional RP1 was allowed if protocol-specified criteria were met. This updated analysis evaluated overall survival (OS) using the Kaplan-Meier (KM) method. Results: Of 140 enrolled pts, 49.3% had stage IVM1b–d disease, 55.7% had PD-L1–negative tumors, 46.4% had prior anti–PD-1 + anti–CTLA-4 therapy, and 65.0% had primary resistance to prior anti–PD-1 (ie, progression within 6 months of starting the immediate prior course of anti–PD-1). The median (95% CI) OS was 32.2 (25.8, 39.2) months (the median OS follow-up was 3 years by reverse KM method). OS rates (95% CI) at 1, 2, and 3 years were 75.3% (66.9%, 81.9%), 61.6% (52.5%, 69.4%), and 45.5% (35.8%, 54.7%), respectively. Importantly, among responders (n=47), the 3-year OS rate (95% CI) was 81.8% (65.2%, 91.0%) vs 22.5% (12.6%, 34.2%) for non-responders (n=93). The 3-year OS rates were 41.8% in pts with stage IVM1b–d disease (n=69), 37.2% for those with PD-L1–negative tumors (n=78), 37.4% in pts with prior anti–PD-1 + anti–CTLA-4 therapy (n=65), and 44.8% in pts with primary resistance to anti–PD-1 (n=91). The safety profile for RP1 + nivo remained consistent with prior reports; no new safety signals were seen. Conclusions: The 3-year landmark OS rate of 45.5% in the overall population and 81.8% among responders provides further evidence that the deep and durable responses provided by RP1 + nivo translate into long term clinical benefit, including extended OS in pts with melanoma post-confirmed progression on prior anti–PD-1–based therapy. Clinical trial information: NCT03767348 .