RP1–nivolumab preserves quality-adjusted survival in melanoma

By Olivia Hart

In 121 patients with advanced cutaneous melanoma whose disease progressed after anti–PD-1 therapy, the phase 1/2 IGNYTE trial (NCT03767348) found a median quality-adjusted overall survival of 26.4 months with intratumoral RP1 plus nivolumab. RP1 is vusolimogene oderparepvec-wtpg (Tudriqev); nivolumab is Opdivo.

Median overall survival (OS) in the same health-related quality-of-life-evaluable cohort was 32.2 months (95% CI, 24.4-39.2). The 1-, 2-, and 3-year OS rates were 74.4%, 60.3%, and 45.7%, respectively.

Median follow-up was 40.0 months (95% CI, 37.5-43.1) by reverse Kaplan-Meier estimation. Patients accrued 2.81 quality-adjusted life-years (QALYs), or 33.7 months, on a restricted-mean basis—92% of the 36.8-month restricted mean OS.

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

The analysis was presented at the 2026 Society for Immunotherapy of Cancer Annual Meeting, Nov. 4-8 in Phoenix. Prior IGNYTE data supported the FDA’s Aug. 6, 2026 accelerated approval of RP1 with nivolumab for adults with unresectable advanced cutaneous melanoma whose disease progressed on a PD-1–blocking antibody-based regimen. The long-term results extend that evidence base.

How did IGNYTE test the combination?

The global, multicenter registrational cohort enrolled 140 patients with cutaneous melanoma whose disease had progressed on prior anti–PD-1 therapy. Eligibility criteria included:

• Confirmed progression on an anti–PD-1 regimen, given alone or with another agent, for at least 8 weeks; that regimen also had to be the patient’s most recent treatment.
• Patients treated in the adjuvant setting had to progress during, rather than after, adjuvant anti–PD-1 therapy.
• Measurable disease, adequate organ function, ECOG performance status of 0 or 1, and no previous oncolytic virus therapy.

Treatment followed a step-up intratumoral schedule:

• The first RP1 dose was 1 × 10⁶ plaque-forming units (PFU)/mL. For cycles 2-8, patients received RP1 at 1 × 10⁷ PFU/mL plus nivolumab at 240 mg every 2 weeks.
• Nivolumab continued at 240 mg for cycle 9 and 480 mg every 4 weeks for cycles 10-30. Protocol-defined criteria allowed RP1 retreatment beyond cycle 8.

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

The population had these baseline features:

• Median age 62 years, with a range of 21-91; 67.9% were male.
• Stage IV M1b/c/d disease accounted for 49.3%; 55.7% had PD-L1–negative tumors.
• 43.6% had received anti–PD-1 therapy with anti–CTLA-4 therapy, and 65.0% had primary resistance to anti–PD-1 therapy.

Efficacy results evolved at the March 8, 2026 data cutoff:

• The primary analysis found an ORR of 32.9%, including a 15.0% complete response rate, and a median DOR of 33.7 months.
• At the later cutoff, ORR was 33.6% and median DOR was 24.8 months. In the full cohort, median OS was 32.9 months (95% CI, 25.8-46.0), and 3-year OS was 47.8%.

How was quality-adjusted survival measured?

Investigators collected EORTC QLQ-C30 responses at baseline and approximately 3 and 6 months. Of 140 patients, 121 (86.4%) had at least one evaluable assessment. A published response-mapping algorithm converted responses to EQ-5D-5L utilities, valued with a UK 5-level tariff in the base case. Utilities were high and stable at 0.896, 0.887, and 0.850 across the three time points.

Investigators carried the final observed utility forward to death or censoring, then summed utility-weighted survival to generate QA-OS. The subset’s survival closely tracked the full cohort, with no more than a 2-percentage-point difference and overlapping 95% CIs. Excluding 19 patients therefore did not appear to introduce meaningful bias.

Against a restricted mean OS reference of 3.07 life-years, sensitivity analyses produced:

• 2.67 QALYs (87%) assuming a linear decline in utility.
• 2.86 QALYs (93%) using baseline utility only.
• 2.81 QALYs (92%) with a PFS-informed approach.
• 2.79 QALYs (91%) with each of two alternative value sets.

What did response status reveal?

Among 42 confirmed responders, median OS was not reached; among 79 nonresponders, it was 16.0 months (95% CI, 10.3-24.4). Three-year OS was 81.3% and 23.6%, respectively.

Observed mean QA-OS was 2.99 QALYs among responders versus 1.24 among nonresponders, an approximately 2.4-fold difference. Restricted mean QA-OS was 4.44 versus 1.53 QALYs, respectively.

Investigators cautioned that the responder analyses were descriptive and could overstate differences because of guarantee-time bias: patients must survive long enough to achieve a response.

What does this change for patients with anti–PD-1–progressed melanoma?

For adults with unresectable advanced cutaneous melanoma progressing after PD-1 blockade, the accelerated-approved RP1–nivolumab regimen now has long-term evidence showing survival accompanied by stable HRQOL. Responders gained substantially more QALYs than nonresponders, but the comparison cannot establish that response causes the survival advantage. As follow-up passes the trial’s 40-month median, the key question is whether quality-adjusted survival continues to track OS without erasing that responder–nonresponder gap.