Replimune RP2 Phase 1 Reports 19% Monotherapy ORR and 19.1% ORR with Nivolumab
REPL•Replimune’s Phase 1 RP2 study in 85 pretreated advanced solid tumor patients showed a 19% ORR monotherapy and 19.1% ORR with nivolumab plus a 48.9% disease control rate. Responses were durable, lasting 35.2 months, and a pooled 33.3% ORR in uveal melanoma prompted initiation of a Phase 2/3 trial.
1. Phase 1 Efficacy Results
Replimune enrolled 85 pretreated advanced solid tumor patients in its Phase 1 first-in-human RP2 trial, reporting a 19.0% ORR for monotherapy (4 of 21 evaluable patients) and a 19.1% ORR with nivolumab (9 of 47), achieving a 48.9% disease control rate in the combination cohort.
2. Durability and Biomarker Insights
Responses were durable, with the monotherapy median duration of response not reached (range: 11.5–27.3+ months) and a 22.1-month median in the combination group (range: 2.8–35.2+ months). Translational analyses revealed RP2 reprogrammed tumors from immunologically cold to inflamed, upregulated T-cell cytotoxicity and antigen presentation, and expanded HSV-1-specific and tumor-associated TCR clones.
3. Safety Findings and Phase 2/3 Launch
RP2 monotherapy and RP2 with nivolumab were well tolerated, with no Grade 4 or 5 treatment-related adverse events and no unexpected toxicities beyond expected immune activation. A pooled 33.3% ORR in uveal melanoma patients has prompted enrollment in a randomized Phase 2/3 trial for metastatic uveal melanoma.
