IGNYTE-3 at a Glance
Key facts
• Design: randomized, open-label, parallel-assignment Phase 3; RP1 (TUDRIQEV) + nivolumab vs treatment of physician's choice (ClinicalTrials.gov).
• Population: unresectable/metastatic Stage IIIb–IV cutaneous melanoma with confirmed progression on anti-PD-1 and anti-CTLA-4 therapy (or anti-PD-1 alone if anti-CTLA-4-ineligible); ages 12+ (ClinicalTrials.gov).
• Enrollment: ~400 planned; started Jul 11, 2024; recruiting (ClinicalTrials.gov).
• Endpoints: primary OS; secondary PFS and ORR per RECIST v1.1 (ClinicalTrials.gov).
• Regulatory stakes: confirmatory trial for TUDRIQEV's Aug 6, 2026 accelerated approval; only ~10% enrolled at approval; OS analysis due by September 2030 (FDA SBRA / OCE Review).
• No efficacy data have been reported. This page tracks status, design, and regulatory stakes only.
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How IGNYTE-3 Is Built
Arms
Experimental: intratumoral RP1 (vusolimogene oderparepvec, a genetically modified HSV-1 oncolytic immunotherapy) + nivolumab. Active comparator - physician's choice (one of, per approved label / local guidelines): nivolumab + relatlimab (Opdualag), anti-PD-1 monotherapy (nivolumab or pembrolizumab), or single-agent chemotherapy (dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel).
Source: ClinicalTrials.gov NCT06264180 →Population
Unresectable or metastatic Stage IIIb–IV (M1a–M1d) cutaneous melanoma, AJCC 8th edition, ages 12 and older. Requires confirmed progression on an anti-PD-1 antibody and an anti-CTLA-4 antibody (combination or sequential), documented by 2 assessments at least 4 weeks apart; patients who are not anti-CTLA-4 candidates in the physician's judgment are eligible after confirmed progression on anti-PD-1 alone. BRAF V600-mutant patients should have received prior BRAF-directed therapy unless contraindicated. At least one measurable tumor ≥1 cm and injectable lesion(s) ≥1 cm required. Excluded: mucosal or uveal melanoma, more than 2 lines of systemic therapy for advanced disease, active CNS metastases, and prior oncolytic-virus or intratumoral therapy.
Source: ClinicalTrials.gov NCT06264180 →Endpoints
Primary: overall survival (time from randomization to death from any cause). Secondary: progression-free survival and objective response rate per RECIST v1.1. No results have been posted.
Source: ClinicalTrials.gov NCT06264180 →The Confirmatory Bar for TUDRIQEV
TUDRIQEV's August 6, 2026 approval in anti-PD-1-failed advanced melanoma came through the accelerated pathway, based on the single-arm IGNYTE study (FDA-adjudicated ORR 24.2%). That makes IGNYTE-3 the trial that decides whether the approval stands: it must verify clinical benefit on overall survival against an active comparator. FDA's own review records set the stakes plainly.
What the FDA record says
• Only about 10% of IGNYTE-3 was enrolled at the time of approval (FDA OCE Review Memorandum).
• The post-marketing requirement sets the overall-survival analysis deadline at September 2030 (FDA Summary Basis for Regulatory Action).
• FDA: failure to verify benefit or to conduct the trial with due diligence “can be grounds for withdrawing approval using expedited withdrawal procedures” (FDA OCE Review Memorandum).
IGNYTE-3 Milestones
Jul 11, 2024 — Study start
First patient activity per ClinicalTrials.gov; randomized enrollment opens across sites (Stanford among early openers, per Dr. Betof Warner).
Aug 6, 2026 — TUDRIQEV accelerated approval
FDA grants accelerated approval based on IGNYTE; IGNYTE-3 becomes the confirmatory post-marketing requirement, with ~10% of patients enrolled at that date (FDA OCE Review).
Sept 2030 — OS analysis due
Post-marketing requirement deadline for the overall-survival analysis (FDA SBRA); ClinicalTrials.gov lists estimated primary completion Sept 30, 2030.
Mar 2031 — Estimated study completion
Per ClinicalTrials.gov (estimated).
What's Being Said About IGNYTE-3
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Frequently Asked Questions
What is the IGNYTE-3 trial?
IGNYTE-3 (RP1-104, NCT06264180) is a randomized, open-label Phase 3 trial comparing intratumoral RP1 (vusolimogene oderparepvec, brand TUDRIQEV) plus nivolumab against treatment of physician's choice in about 400 patients with unresectable or metastatic cutaneous melanoma that progressed on both an anti-PD-1 and an anti-CTLA-4 antibody. The primary endpoint is overall survival.
Is IGNYTE-3 the same trial as IGNYTE?
No. IGNYTE (NCT03767348) is the completed single-arm Phase 1/2 study whose melanoma cohort supported TUDRIQEV's accelerated approval on August 6, 2026. IGNYTE-3 is the separate, ongoing randomized Phase 3 confirmatory trial. IGNYTE-3 has reported no efficacy data yet.
What can patients in the physician's-choice arm receive?
The investigator selects one option consistent with the approved label or local guidelines: nivolumab plus relatlimab (Opdualag), anti-PD-1 monotherapy (nivolumab or pembrolizumab), or single-agent chemotherapy (dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel).
Why does IGNYTE-3 matter for TUDRIQEV's approval?
TUDRIQEV's August 6, 2026 approval came through the accelerated pathway, so continued approval may be contingent on IGNYTE-3 verifying clinical benefit. FDA noted only about 10% of the trial was enrolled at approval and that failure to conduct the trial with due diligence can be grounds for withdrawing approval using expedited withdrawal procedures.
When will IGNYTE-3 results be available?
ClinicalTrials.gov lists estimated primary completion on September 30, 2030, with study completion estimated March 31, 2031. The trial began July 11, 2024 and is recruiting.
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated September 3, 2026.