Replimune Group, Inc. announced updated data from the first 75 patients in the anti-PD1 failed melanoma cohort of the IGNYTE clinical trial along with data from the ongoing Phase 1 trial of RP2 combined with nivolumab in patients with uveal melanoma are being presented at the ASCO annual meeting. The anti-PD1 failed melanoma cohort of the IGNYTE clinical trial evaluating RP1 (vusolimogene oderparepvec) in combination with nivolumab is registration-directed. Updated Data from the IGNYTE Clinical Trial Cohort Evaluating RP1 Combined with Nivolumab in anti-PD1 Failed Melanoma: IGNYTE is Replimune's multi-cohort clinical trial evaluating RP1 combined with nivolumab in multiple tumor type specific cohorts.

The anti-PD1 failed melanoma cohort is registration-directed and completed enrollment earlier in the year with 141 patients enrolled. These updated data include the first 75 patients from the anti-PD1 failed melanoma cohort combined with the 16 anti-PD1 failed melanoma patients from the prior all comers 30 patient melanoma cohort (n=91 in total). The IGNYTE clinical trial is being conducted under a collaboration and supply agreement with Bristol Myers Squibb.

With a median follow up of 75.9 weeks, the updated data show an overall objective response rate (ORR) of 37.4% (37.5% in the 16 patients from the prior cohort, 37.3% in the 75 patients from the new cohort), with an ORR of at least 28.3% in all subgroups analyzed, including in patients: Having failed anti-CTLA-4 therapy as well as anti-PD1 therapy (34.4% ORR, n=32), With Stage IVM1b/c disease (28.3% ORR, n=46), Who progressed while on prior adjuvant anti-PD1 therapy (50% ORR, n=32); patients who progressed after stopping adjuvant therapy were not eligible for the trial, With both primary refractory (36.0% ORR, n=50) and secondary refractory (42.1% ORR, n=38) disease; The data show systemic activity, with both injected and in un-injected lesions responding with similar durability and kinetics, including in un-injected visceral disease. From when last reported in December 2022, all responding patients remain in response, further highlighting the duration of benefit; 85% of responses are ongoing with 71% of responders out over one year from starting therapy; Patients with up to >20cm of total disease responded, including patients with up to >10cm of uninjected disease; Updated analyses demonstrate activity in patients with PD-L1 negative tumors as well as those whose tumors were PD-L1 positive and with both BRAF wild type and BRAF mutant disease; Analysis of PFS and ORR for the population as a whole and broken down by prognostic and other factors was also provided. This demonstrated that PFS and OS are most strongly impacted by response to RP1 combined with nivolumab, but not impacted by whether all lesions were or were not injected with RP1.

Other factors assessed (disease stage, prior treatment setting [adjuvant vs not adjuvant prior anti-PD1], prior anti-CTLA-4 or no prior anti-CTLA-4) had only a more modest impact on progression-free survival (PFS) and overall survival (OS); RP1 continues to be generally well tolerated with safety data showing predominantly ‘on target' flu-like Grade 1-2 side effects indicative of systemic immune activation. Grade 3 treatment related events were rarely seen in the 91-patient group, with a range of Grade 3 events in one patient each, and two Grade 3 events of fatigue. There were two Grade 4 treatment related events (elevated lipase, and cytokine release syndrome) and no treatment related Grade 5 events.