Poster Presentation Australasian Melanoma Conference 2026

A randomized, controlled, multicenter, phase 3 study of RP1 (vusolimogene oderparepvec) combined with nivolumab vs physician’s choice of therapy in patients with advanced melanoma that has progressed on anti–PD-1 and anti–CTLA-4 therapy (IGNYTE-3) (#327)

Shahneen K. Sandhu 1 , Yana G. Najjar 2 , Caroline Robert 3 , Nikhil I. Khushalani 4 , Michael K. Wong 5 , Tawnya Lynn Bowles 6 , Paolo A. Ascierto 7 , Georgina V. Long 8 , Dirk Schadendorf 9 , Allison Betof 10 , Gregory A. Daniels 11 , Gino K. In 12 , Frances Collichio 13 , Ardy Davarifar 14 , Yvonne M. Saenger 15 , Suthee Rapisuwon 16 , Ryan M. Weight 17 , Giuseppe Gullo 18 , Marcus Viana 18 , Mark Navarro 18 , Omid Hamid 19
  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. UPMC Hillman Cancer Center, Pittsburgh, PA, USA
  3. Gustave Roussy and Paris-Saclay University, Villejuif, France
  4. Moffitt Cancer Center, Tampa, FL, USA
  5. Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
  6. Intermountain Medical Center, Murray, UT, USA
  7. Melanoma and Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
  8. Melanoma Institute Australia, The University of Sydney, Royal North Shore Hospital, and Mater Hospital, Sydney, NSW, Australia
  9. Department of Dermatology, West German Cancer Center, University Hospital Essen, & National Center for Tumor Diseases (NCT-West), Campus Essen, & University Alliance Ruhr, Research Alliance Ruhr, Research Center One Health, University Duisburg-Essen, Essen, Germany
  10. Stanford University School of Medicine, Stanford, CA, USA
  11. Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
  12. University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  13. Division of Oncology, University of North Carolina, Chapel Hill, NC, USA
  14. University of Tennessee Medical Center, Knoxville, TN, USA
  15. Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA
  16. MedStar Georgetown Cancer Institute, Washington, DC, USA
  17. The Melanoma and Skin Cancer Institute, Englewood, CO, USA
  18. Replimune, Inc., Woburn, MA, USA
  19. The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA, USA

Background: Melanoma is the fifth most common cancer, with over 110,000 new cases and 8500 related deaths projected in the US for 2026. First-line systemic treatment with immune checkpoint inhibitors improves the objective response rate (ORR) and extends progression-free survival (PFS) and overall survival (OS) for patients with advanced disease. Among available treatments, combination anti–PD-1 (nivolumab) + anti–CTLA-4 (ipilimumab) therapy is associated with the highest ORR and best PFS and OS. However, only around half of patients respond to treatment, and limited options exist for patients whose melanoma progresses following anti–PD-(L)1 ± anti–CTLA-4 therapy. RP1 (vusolimogene oderparepvec) is an HSV-1–based oncolytic immunotherapy that expresses human granulocyte-macrophage colony-stimulating factor and a fusogenic glycoprotein (GALV-GP-R−). IGNYTE-3 will evaluate the OS and clinical benefit of RP1 + nivolumab for patients with advanced cutaneous melanoma whose disease has progressed after anti–PD-1 and anti–CTLA-4 therapy (or who are ineligible for anti–CTLA-4 therapy) vs physician’s choice. RP1 + nivolumab previously demonstrated durable, clinically meaningful anti-tumor activity (ORR, 33.6% per independent central review), with minimal toxicity in a phase 2 registrational cohort of patients with advanced melanoma and confirmed progression on prior anti–PD-1 therapy (NCT03767348). Repetitive intralesional, including intravisceral, injections were well tolerated.

Methods: IGNYTE-3 (NCT06264180) is a global, randomized, controlled, phase 3 trial. Key eligibility criteria include age ≥12 years, stage IIIB–IVM1a–M1d cutaneous melanoma, disease progression on ≥12 weeks of anti–PD-1 + anti–CTLA-4 treatment (administered in combination or in sequence, with anti–PD-1 last), ≥1 measurable and injectable tumor, and adequate hematologic, hepatic, and renal function. Patients who are not candidates for anti–CTLA-4 therapy may enroll following progression on anti–PD-1 therapy alone. Patients with BRAF V600-mutant melanoma should have received anti-BRAF ± anti-MEK–targeted therapy prior to enrollment, where appropriate. Patients (N ≈ 400) will receive RP1 + nivolumab or physician’s choice (nivolumab + relatlimab, anti–PD-1 monotherapy rechallenge [nivolumab or pembrolizumab], or single-agent chemotherapy [dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel]). The primary endpoint of the study is OS; the key secondary endpoints are PFS and ORR per RECIST 1.1.