Replimune Group (REPL) Study Result summary

Study design and patient population

• IGNITE/IGNYTE is a global Phase I/II trial of RP1 plus nivolumab in anti-PD-1 failed melanoma, enrolling a real-world, hard-to-treat population with stringent eligibility criteria and 156 participants.

• Nearly half of patients had visceral disease, two-thirds had primary refractory disease, and one-third had high LDH, indicating high risk.

• All patients had confirmed progression on prior anti-PD-1 therapy and at least 12 months of follow-up; median follow-up was 15.4 months.

• Primary endpoint was overall response rate (ORR) by central review using mRECIST 1.1.

• RP1 is an oncolytic immunotherapy based on a genetically engineered herpes simplex virus designed for local and systemic anti-tumor activity.

Efficacy and safety results

• Central review showed an ORR of 33.6% by mRECIST 1.1 and 32.9% by RECIST 1.1, both exceeding historical response rates of 6-7%.

• Median duration of response exceeded 36 months, with all responses lasting more than 6 months.

• Responses were observed in both injected and non-injected lesions, including visceral and bone metastases, indicating systemic benefit.

• RP1 plus nivolumab was well tolerated, with most adverse events being grade 1/2 constitutional symptoms, low incidence of grade 3/4 events, and no grade 5 events.

• Most common side effects included chills, fatigue, pyrexia, and nausea.

Subgroup and case highlights

• Subgroup analysis showed a 27% ORR in patients who failed both ipilimumab and nivolumab, and 34% in those with primary resistance to anti-PD-1.

• 1 in 3 patients achieved an objective response, with 55% experiencing clinical benefit (CR + PR + SD).

• Deep and durable responses were seen across disease stages, including complete responses in advanced disease.

• Case studies demonstrated complete systemic responses, including clearance of distant and visceral metastases.