Poster Presentation Australasian Melanoma Conference 2026

A randomized, phase 2/3 clinical trial investigating RP2 plus nivolumab vs ipilimumab plus nivolumab in immune checkpoint inhibitor–naïve patients with metastatic uveal melanoma (#319)

Georgina V. Long 1 , Marlana M. Orloff 2 , Justin C. Moser 3 , Alexander N. Shoushtari 4 , Allison Betof 5 , Diwakar Davar 6 , Sunandana Chandra 7 , Alexandra Ikeguchi 8 , April K.S. Salama 9 , Ryan J. Sullivan 10 , Shaheer Khan 11 , Sapna P. Patel 12 , Anthony M. Joshua 13 , Jessica C. Hassel 14 , Mayowa Agbaje-Williams 15 , Mark Navarro 15 , Rahul Marpadga 15 , Giuseppe Gullo 15 , Joseph J. Sacco 16
  1. Melanoma Institute Australia, The University of Sydney, Royal North Shore Hospital, and Mater Hospital, Sydney, NSW, Australia
  2. Thomas Jefferson University Hospital, Philadelphia, PA, USA
  3. HonorHealth Research Institute, Scottsdale, AZ, USA
  4. Memorial Sloan Kettering Cancer Center, New York, NY, USA
  5. Stanford University School of Medicine, Stanford, CA, USA
  6. UPMC Hillman Cancer Center, Pittsburgh, PA, USA
  7. Northwestern University, Chicago, IL, USA
  8. The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  9. Department of Medicine, Division of Medical Oncology, Duke University, Durham, NC, United States
  10. Massachusetts General Hospital, Boston, Massachusetts, USA
  11. Northwell Health Cancer Institute, New Hyde Park, NY, USA
  12. University of Colorado Cancer Center, Aurora, CO, USA
  13. Kinghorn Cancer Centre, St Vincent’s Hospital and Garvan Institute of Medical Research, Sydney, NSW, Australia
  14. University Hospital Heidelberg, Heidelberg, Germany
  15. Replimune, Inc., Woburn, MA, USA
  16. The Clatterbridge Cancer Centre and University of Liverpool, Wirral and Liverpool, UK

Background: Uveal melanoma (UM) is the most common primary intraocular malignancy. Half of patients with UM develop metastases, most commonly in the liver (~90%). Prognosis is poor, with a median OS for metastatic UM (mUM) of ~1 year. Effective treatment options are limited, as mUM responds poorly to single-agent immune checkpoint inhibitors (ICIs; <10% response rate). Combination therapies have slightly higher response rates (12%−18%) but often have increased toxicity. Tebentafusp is FDA-approved for mUM but is restricted to patients who are HLA-A*02:01 positive, and only ~10% of patients achieve an objective response. RP2 is a selectively replication-competent HSV-1–based oncolytic immunotherapy expressing human GM-CSF, a fusogenic glycoprotein (GALV-GP-R−), and an anti–CTLA-4 antibody-like molecule. Preliminary clinical data of intratumoral RP2 ± nivolumab demonstrated a promising safety profile and anti-tumor activity with an ORR of 29.4% and DCR of 58.8% in 17 patients with mUM, most of whom had received prior ICIs. This study will assess the efficacy and safety of RP2 + nivolumab vs ipilimumab + nivolumab in patients with ICI-naïve mUM.

 

Methods: This is a multicenter, randomized, controlled, phase 2/3 study (NCT06581406; RP2-202). Eligible patients are ≥18 years of age with confirmed unresectable mUM with ≥1 lesion amenable to injection; ≤1 prior line of therapy in the metastatic setting is allowed. Patients with prior exposure to ICIs since diagnosis, >50% liver involvement, or previous selected liver-directed therapies are not eligible. Enrolled patients (N=~280) will be randomized 1:1 to receive either RP2 + nivolumab or ipilimumab + nivolumab. In the RP2 + nivolumab arm, RP2 will be given intratumorally at 1×106 PFU/mL (×1), then Q2W at 1×107 PFU/mL (×7) + intravenous (IV) nivolumab (240mg). In the ipilimumab + nivolumab arm, patients will receive IV ipilimumab (3mg/kg) and IV nivolumab (1mg/kg) Q3W for 4 doses. Patients in both arms may receive IV nivolumab (240mg Q2W or 480mg Q4W) for up to 2 years. The co-primary endpoints are OS and PFS by independent central review using RECIST 1.1. Secondary endpoints are ORR, DOR, DCR, clinical benefit rate, duration of clinical benefit, and safety, including incidence of TRAEs, serious AEs, and immune-mediated AEs.