RP1 Plus Nivolumab Preserves Quality-Adjusted Survival in Advanced Melanoma After Anti–PD-1 Therapy

Treatment with vusolimogene oderparepvec-wtpg (Tudriqev; RP1) plus nivolumab (Opdivo) generated durable overall survival (OS) that was largely spent with preserved health-related quality of life (HRQOL) in patients with advanced melanoma who progressed on prior anti–PD-1 therapy, according to long-term OS and quality-adjusted OS (QA-OS) data from the phase 1/2 IGNYTE trial (NCT03767348) presented at the 2026 SITC Annual Meeting.¹

Patients who responded to the combination accrued markedly more quality-adjusted life-years (QALYs) than those who did not respond, and the findings held across multiple sensitivity analyses and alternative value sets.

Findings showed that in the HRQOL-evaluable cohort (n = 121), the median OS was 32.2 months (95% CI, 24.4-39.2), and the median QA-OS was 26.4 months. The 1-, 2-, and 3-year OS rates were 74.4%, 60.3%, and 45.7%, respectively. Patients accrued a restricted mean QA-OS of 2.81 QALYs (33.7 months), which amounted to 92% of the 36.8-month restricted mean OS. The median follow-up by reverse Kaplan-Meier estimate was 40.0 months (95% CI, 37.5-43.1).

"Collectively, these findings support the value of RP1 plus nivolumab as a well-tolerated therapy that improves OS and also can preserve QOL," said lead study author Gino K. In, MD, MPH, of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles.

Prior data from IGNYTE supported the August 2026 FDA accelerated approval of RP1 in combination with nivolumab for the treatment of adult patients with unresectable advanced cutaneous melanoma who experienced disease progression on a PD-1–blocking antibody–based regimen.²

How was the IGNYTE trial designed?

The registrational cohort of the global, multicenter IGNYTE trial enrolled 140 patients with cutaneous melanoma whose disease had progressed on prior anti–PD-1 therapy.¹ To qualify, patients needed confirmed progression on an anti–PD-1–based regimen, given alone or in combination, for 8 weeks or longer, and that regimen had to be their most recent treatment. Those previously treated in the adjuvant setting must have progressed during, rather than after, adjuvant anti–PD-1 therapy. Patients also needed measurable disease, adequate organ function, and an ECOG performance status of 0 or 1, and could not have previously received oncolytic virus therapy.

Patients received a first intratumoral dose of RP1 at 1 × 10⁶ plaque-forming units (PFU)/mL, followed by RP1 at 1 × 10⁷ PFU/mL plus nivolumab at 240 mg every 2 weeks for cycles 2 through 8. Nivolumab was then continued at 240 mg for cycle 9 and at 480 mg every 4 weeks for cycles 10 through 30; retreatment with RP1 beyond 8 cycles was permitted under protocol-defined criteria.

Safety and objective response rate (ORR) by modified RECIST 1.1 criteria per independent central review were the primary end points. Secondary end points included ORR by investigator assessment; duration of response (DOR), complete response (CR) rate, disease control rate, and progression-free survival (PFS); and 1- and 2-year OS.

The median patient age was 62 years (range, 21-91), and 67.9% of patients were male. Overall, 49.3% of patients had stage IVM1b/c/d disease, 55.7% had PD-L1–negative tumors, 43.6% had received anti–PD-1 therapy in combination with anti–CTLA-4 therapy, and 65.0% had primary resistance to anti–PD-1 therapy.

In the primary analysis, the ORR was 32.9%, including a CR rate of 15.0%, and the median DOR was 33.7 months. As of a March 8, 2026, data cutoff, the ORR was 33.6%, the median DOR was 24.8 months, and the 3-year OS rate in the full cohort was 47.8%, with a median OS of 32.9 months (95% CI, 25.8-46.0).

How was QA-OS measured?

Investigators collected EORTC QLQ-C30 responses at baseline and at approximately 3 and 6 months; 121 of 140 patients (86.4%) had at least 1 evaluable assessment and were included in the QA-OS analysis. Responses were mapped to EQ-5D-5L utilities using a published response-mapping algorithm and valued with a UK 5-level tariff as the base case. Utilities were high and stable over time, at 0.896, 0.887, and 0.850 across the 3 time points. The final observed utility was carried forward to death or censoring, and utility-weighted survival time was then summed to generate QA-OS.

Survival outcomes in the HRQOL-evaluable subset closely tracked those of the full cohort, differing by no more than 2 percentage points with overlapping 95% CIs, which suggested that excluding 19 patients did not meaningfully bias the analysis. Against a restricted mean OS reference of 3.07 life-years, QA-OS ranged from 2.67 QALYs (87%) when assuming a linear decline in utility to 2.86 QALYs (93%) when using baseline utility only; a PFS-informed approach yielded 2.81 QALYs (92%), and 2 alternative value sets each yielded 2.79 QALYs (91%).

How did outcomes differ by response?

Among confirmed responders (n = 42), the median OS was not reached compared with 16.0 months (95% CI, 10.3-24.4) among nonresponders (n = 79). The 3-year OS rates were 81.3% and 23.6%, respectively.

The observed mean QA-OS reached 2.99 QALYs among responders compared with 1.24 QALYs among nonresponders, an approximately 2.4-fold difference. The restricted mean QA-OS was 4.44 QALYs vs 1.53 QALYs, respectively. Investigators cautioned that the responder analyses were descriptive and may be skewed toward responders by guarantee-time bias, because patients must live long enough to achieve a response.

References

1. Schadendorf D, Bowles TL, Sacco JJ, et al. 3-Year landmark overall survival and quality-adjusted overall survival with RP1 combined with nivolumab in anti–PD-1–failed melanoma: results from the IGNYTE trial. Paper presented at: 2026 Society for Immunotherapy of Cancer Annual Meeting; November 4-8, 2026; Phoenix, AZ
2. FDA grants accelerated approval to vusolimogene oderparepvec-wtpg in combination with nivolumab for melanoma. FDA. August 6, 2026. Accessed August 6, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-vusolimogene-oderparepvec-wtpg-combination-nivolumab-melanoma