RP1/Nivolumab Shows OS Benefit in Anti-PD-1-Progressed Melanoma

Deep and durable responses were noted with vusolimogene oderparepvec (RP1) plus nivolumab (Opdivo) for patients with advanced melanoma who had progression on anti-PD-1 therapy, according to the 3-year survival analysis of the phase 3 IGNYTE trial (NCT03767348), which was presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and Exposition.¹

The median overall survival (OS) was 32.9 months (95% CI, 25.8-46.0), with a 1-year OS rate of 75.3% (95% CI, 66.9%-81.9%), a 2-year rate of 61.5% (95% CI, 52.4%-69.4%), and a 3-year rate of 47.8% (95% CI, 38.6%-56.5%). The median OS was not reached (NR; 95% CI, NR-NR) among responders and 18.5 months (95% CI, 12.8-24.5) among non-responders.

OS rates for responders and non-responders were 97.9% (95% CI, 85.8%-99.7%) vs 62.4% (95% CI, 51.0%-71.9%) at 1 year, 95.7% (95% CI, 84.0%-98.9%) vs 41.2% (95% CI, 30.2%-51.8%) at 2 years, and 83.5% (95% CI, 68.5%-91.8%) vs 26.4% (95% CI, 16.9%-36.9%) at 3 years.

Across subgroups, the OS benefit was 39.2 months (95% CI, 27.6-NR) for those with stage IIIB/IIIC/IVM1a disease vs 27.6 months (95% CI, 12.9-37.4) for those with stage IVM1b/c/d; NR (95% CI, 32.2-NR) for those who were PD-L1 positive vs 25.8 months (95% CI, 18.6-36.1) for those who were PD-L1 negative; 46.0 months (95% CI, 28.9-NR) for those who had not received prior anti-CTLA-4 compared with 18.6 months (95% CI, 12.9-37.1) for those who had; and 32.9 months (95% CI, 22.8-48.9) for those with primary resistance vs 34.7 months (95% CI, 20.1-NR) for those with secondary resistance.

The median duration of response (DOR) was 24.8 months (95% CI, 14.8-NR). The 1-year DOR rate was 72.3%, the 2-year rate was 51.4%, and the 3-year rate was 44.8%. The overall response rate (ORR) was 33.6% (95% CI, 25.8%-42.0%). The median progression-free survival (PFS) was 3.6 months (95% CI, 2.0-5.0); for responders, it was 34.9 months (95% CI, 22.0-NR).

“RP1 plus nivolumab had a long-term clinical benefit, a consistent benefit across clinically relevant subgroups, and continues to demonstrate a favorable safety profile,” Michael K. Wong, MD, PhD, FRCPC, physician-in-chief at Roswell Park Comprehensive Cancer Center, said during the presentation.

A total of 140 patients were enrolled in the trial. Patients were screened, then 28 days later received cycle 1, which was RP1 at 10⁶ PFU/mL; 2 weeks later, cycles 2 through 8 were initiated, which included RP1 at 1 x 10⁷ PFU/mL plus nivolumab at 240 mg. After a 2-week interval, cycle 9 began with nivolumab at 240 mg, followed by another 2-week interval, then cycles 10 through 30, which were nivolumab at 480 mg every 4 weeks. At 100 days, a safety follow-up was conducted.

Patients were enrolled if they had melanoma with progression on prior anti-PD-1 therapy, measurable disease, adequate organ function, no prior oncolytic therapy, and an ECOG performance status of 0 to 1.

The criteria for having a PD-1 agent fail a patient included confirmed progression while being treated with at least 8 weeks of anti-PD-1 therapy alone or in combination; the anti-PD-1 must be the last prior therapy. Those on prior adjuvant therapy were required to have confirmed progression while being treated with adjuvant therapy.

The median patient age was 62 years; 67.9% of patients were male, the most notable stage was IVM1b/c/d in 49.3% of patients, and 63.6% of patients had BRAF wild-type status. Additionally, 55.7% of patients had PD-L1 negative expression, 43.6% had anti-PD-1 therapy combined with an anti-CTLA-4, and 65.0% had primary resistance.

The primary end point was safety and efficacy via mRECIST by independent central review. Secondary end points included ORR, DOR, complete response rate, PFS, and 1- and 2-year OS rates.

Any-grade treatment-related adverse effects (TRAEs) occurred in 88.7% of patients vs 12.8% for grades 3/4. The most common any-grade TRAEs were chills (31.9%), fatigue (31.9%), pyrexia (30.5%), and nausea (22.7%). The most common grade 3/4 TRAEs were fatigue (0.7%), diarrhea (0.7%), asthenia (0.7%), arthralgia (07%), and decreased appetite (0.7%). There were no grade 5 events.

In April 2026, a second complete response letter was issued by the FDA for the combination because the data from the IGNYTE trial were insufficient and did not show substantial evidence of RP1 effectiveness for the patient population.²

References

1. Wong MKK, Sacco JJ, In GK, et al. A 3-year landmark overall survival analysis of RP1 plus nivolumab in patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial. J Clin Oncol. 2026;44(suppl 16):9518. doi:10.1200/JCO.2026.44.16_suppl.9518
2. Complete response. April 10, 2026. FDA. Accessed May 31, 2026. https://tinyurl.com/ys3etmrj