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.

TPS9598 Background: Uveal melanoma (UM) is the most common primary intraocular malignancy, accounting for ~90% of ocular melanomas and 5% of all melanomas. Half of patients with UM develop metastases, most commonly in the liver (~90%). The prognosis for patients with metastatic UM (mUM) is poor, with a median overall survival (OS) of ~1 year. Effective treatment options for mUM are limited, as it responds poorly to single-agent immune checkpoint inhibitors (ICIs; 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 initially at 1 × 10 6 plaque-forming units (PFU)/mL, then every 2 weeks (Q2W) at 1 × 10 7 PFU/mL for 7 doses in combination with intravenous (IV) nivolumab (240 mg). In the ipilimumab + nivolumab arm, patients will receive IV ipilimumab (3 mg/kg) and IV nivolumab (1 mg/kg) Q3W for 4 doses. Patients in both arms may then receive IV nivolumab at 240 mg Q2W or 480 mg Q4W for up to 2 years. The co-primary endpoints are OS and progression-free survival by independent central review using RECIST 1.1. Secondary endpoints are ORR, duration of response, disease control rate, clinical benefit rate, duration of clinical benefit, and safety, including incidence of treatment-emergent adverse events (AEs), serious AEs, and immune-mediated AEs. Clinical trial information: NCT06581406 .