IGNYTE
RP1 (vusolimogene oderparepvec) in combination with nivolumab in advanced anti-PD-1-failed melanoma: IGNYTE (ClinicalTrials.gov NCT03767348)
Phase 2N = 140NCT03767348
- Population
- Adults with advanced melanoma and confirmed progression on anti-PD-1 therapy of at least 8 weeks, as the last prior treatment. Of 140 patients enrolled: 48.6% stage IVM1b/c/d, 65.7% primary anti-PD-1 resistance, 56.4% PD-L1 negative, 46.4% prior anti-PD-1 and anti-CTLA-4 therapy.
- Design
- Single-arm, open-label, multiregional trial (FDA description); the journal reports the registrational phase 2 cohort of the phase 1/2 IGNYTE study. RP1 intratumoral, up to 8 doses of up to 10 mL, with nivolumab for up to 2 years. Primary endpoint of that cohort: objective response rate by blinded independent central review using modified RECIST 1.1 (journal full text; the FDA label also names ORR as the primary efficacy outcome).
- Primary endpoint
- ORR
- Arms
- RP1 plus nivolumab (experimental, n = 140): RP1 intratumoral (up to 8 doses, up to 10 mL per dose) with nivolumab (up to 2 years)
- People
- Wong MK, senior author Robert C
Show the numbers
| Endpoint | Analysis | RP1 plus nivolumab | Control | Effect |
|---|---|---|---|---|
| ORRAll 140 patients enrolled and treated; single-arm, not described as ITTConfirmed objective response rate by blinded independent central review per RECIST 1.1 (reported alongside the primary modified-RECIST analysis) | primaryWong 2025 | 32.9% (25.2–41.3%) | — | 15.0% complete response (21 of 140). Median follow-up at the primary analysis 15.5 months (range 0.5 to 47.6); data cutoff 8 March 2024. The journal's primary endpoint, ORR by modified RECIST, is a separate Result. |
| ORRAll 140 patients enrolled and treated; single-arm, not described as ITTObjective response rate by blinded independent central review using modified RECIST 1.1 (the primary end point of the registration-intended cohort; progression had to be confirmed by further tumour increase) | primarymedian follow-up 15.5 monthsWong 2025 | 33.6% (25.8–42.0%) | — | Reported in the full text only; the abstract gives the RECIST 1.1 value (32.9%). |
| DORResponders in the journal analysisMedian duration of response (secondary end point; RECIST 1.1, blinded independent central review) | primaryWong 2025 | median 33.7 months | — | 95% CI 14.1 months to not reached (not stored as a numeric interval). Responders in the journal analysis (RECIST 1.1). Median follow-up at the primary analysis 15.5 months (full text). |
| OSPatients enrolled (140)Overall survival rates at 1 and 2 years (secondary end points) | primaryWong 2025 | 75.3% at 12 mo (66.9–81.9%); 63.3% at 2 y (53.6–71.5%) | — | The journal states median overall survival was not reached. |
| ORRFDA efficacy population: 91 of the 140 patients, those with at least one noninjected lesionObjective response rate in the FDA efficacy-evaluable population | primarySource 2026 | 24.2% (15.8–34.3%) | — | Source is the FDA prescribing information (section 14, Table 3, N=91, primary efficacy outcome ORR, 95% CI as printed (15.8, 34.3)); the same values appear on the FDA approval notice. The 91-patient population differs from the journal analysis (all 140 patients, RECIST 1.1 by blinded independent central review); the two ORR values are not interchangeable and the documents do not reconcile them. |
| DORFDA efficacy population: 91 of the 140 patients, those with at least one noninjected lesionMedian duration of response (secondary outcome) in the FDA efficacy population | primarySource 2026 | median 14.1 months | — | Prescribing information Table 3: median DoR 14.1 months (95% CI 10.7, NR), range 3.9 to 34.6+ months, estimated by Kaplan-Meier; not stored as a numeric interval. |
| Endpoint | Analysis | RP1 plus nivolumab | Control | Effect |
|---|---|---|---|---|
| ORRAll 140 patients enrolled and treated; single-arm, not described as ITTConfirmed objective response rate by blinded independent central review per RECIST 1.1 (reported alongside the primary modified-RECIST analysis) | primaryWong 2025 | 32.9% (25.2–41.3%) | — | 15.0% complete response (21 of 140). Median follow-up at the primary analysis 15.5 months (range 0.5 to 47.6); data cutoff 8 March 2024. The journal's primary endpoint, ORR by modified RECIST, is a separate Result. |
| ORRAll 140 patients enrolled and treated; single-arm, not described as ITTObjective response rate by blinded independent central review using modified RECIST 1.1 (the primary end point of the registration-intended cohort; progression had to be confirmed by further tumour increase) | primarymedian follow-up 15.5 monthsWong 2025 | 33.6% (25.8–42.0%) | — | Reported in the full text only; the abstract gives the RECIST 1.1 value (32.9%). |
| DORResponders in the journal analysisMedian duration of response (secondary end point; RECIST 1.1, blinded independent central review) | primaryWong 2025 | median 33.7 months | — | 95% CI 14.1 months to not reached (not stored as a numeric interval). Responders in the journal analysis (RECIST 1.1). Median follow-up at the primary analysis 15.5 months (full text). |
| OSPatients enrolled (140)Overall survival rates at 1 and 2 years (secondary end points) | primaryWong 2025 | 75.3% at 12 mo (66.9–81.9%); 63.3% at 2 y (53.6–71.5%) | — | The journal states median overall survival was not reached. |
| ORRFDA efficacy population: 91 of the 140 patients, those with at least one noninjected lesionObjective response rate in the FDA efficacy-evaluable population | primarySource 2026 | 24.2% (15.8–34.3%) | — | Source is the FDA prescribing information (section 14, Table 3, N=91, primary efficacy outcome ORR, 95% CI as printed (15.8, 34.3)); the same values appear on the FDA approval notice. The 91-patient population differs from the journal analysis (all 140 patients, RECIST 1.1 by blinded independent central review); the two ORR values are not interchangeable and the documents do not reconcile them. |
| DORFDA efficacy population: 91 of the 140 patients, those with at least one noninjected lesionMedian duration of response (secondary outcome) in the FDA efficacy population | primarySource 2026 | median 14.1 months | — | Prescribing information Table 3: median DoR 14.1 months (95% CI 10.7, NR), range 3.9 to 34.6+ months, estimated by Kaplan-Meier; not stored as a numeric interval. |
- RP1 plus nivolumab (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | RP1 plus nivolumab |
|---|---|
| 0 | 100.0% |
| 21 | 64.9% |
| 42 | 42.2% |
| 63 | 27.4% |
| 84 | 17.8% |
- RP1 plus nivolumab (experimental)
Data table (modelled values)
| Months | RP1 plus nivolumab |
|---|---|
| 0 | 100.0% |
| 6 | 86.9% |
| 13 | 73.9% |
| 19 | 67.7% |
| 26 | 63.3% |
Appears in
Sources
Wong MK, Milhem MM, Sacco JJ, Michels J, In GK, Muñoz Couselo E, et al. RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE). J Clin Oncol. 2025;43(33):3589-3599.
US Food and Drug Administration, CBER. TUDRIQEV (vusolimogene oderparepvec-wtpg) prescribing information; 'Initial U.S. Approval: 2026', revised 8/2026.