BLA is filed at FDA for accelerated approval for vusolimogene oderparepvec (RP1 ) + nivolumab (Opdivo) to treat advanced melanoma- Replimune

It was also announced that the FDA granted the breakthrough therapy designation to RP1 with nivolumab in patients with advanced melanoma.

The treatment will undergo confirmatory analysis in the randomized, multicenter, open-label phase IIII IGNYTE-3 trial (NCT06264180), which will monitor RP1 in combination with nivolumab in patients with advanced melanoma who progressed on anti–PD-1 and anti–CTLA-4 therapy. The trial is still currently enrolling patients.

The decision to assign the breakthrough therapy designation was aided by data from the anti–PD-1 failed melanoma cohort in the open-label, dose-escalation and dose-expansion phase 1/II IGNYTE trial (NCT03767348). In the IGNYTE trial, the confirmed objective response rate (ORR) with RP1/nivolumab per independent review committee assessment was 33.6% based on modified RECIST v1.1 criteria; complete responses occurred in 15.0%. Additionally, the ORR was 34.4% in those with primary anti–PD-1 resistance and 26.2% among those previously treated with anti–PD-1 plus anti–CTLA-4 therapy. At 1 and 2 years, respectively, the overall survival (OS) rates were 75.3% (95% CI, 66.9%-81.9%) and 63.3% (95% CI, 53.6%-71.5%). The median OS was not reached at the time of analysis. Grade 3 or higher treatment-related adverse effects occurred in 12.8% of patients, and most toxicities were grades 1 or 2. Investigators observed no RP1-related deaths.

Patients in the IGNYTE-3 trial will be randomly assigned into 1 of 2 trial arms. The experimental arm will consist of treatment of vusolimogene oderparepvec with nivolumab.   The comparator arm will be investigator’s choice of treatment: either nivolumab and relatlimab (Opdualag); an anti–PD-1 monotherapy consisting of nivolumab or pembrolizumab (Keytruda); or single-agent chemotherapy with dacarbazine, temozolomide (Temodar), or paclitaxel. The primary end point will be OS assessed up to approximately 55 months. Secondary endpoints will be progression-free survival and ORR per RECIST v1.1 criteria. Eligibility criteria include patients with histologically or cytologically confirmed unresectable or metastatic stage IIIb to IV/M1a through M1d cutaneous melanoma, confirmed disease progression on an anti–PD-1 and an anti–CTLA-4 treatment, documented BRAF V600mutation status, and an ECOG score of 0 or 1. Grounds for trial exclusion are primary mucosal or uveal melanoma, more than 2 lines of systemic therapy for advanced melanoma, known acute or chronic hepatitis, known human immunodeficiency virus, history of significant cardiac disease, and known active central nervous system metastases, among other factors.

The study has 3 separate phases: a 28-day screening period, a treatment period up to approximately 2 years, and a follow-up period up to 3 years after the completion of treatment. RP1 dosing begins on day 1 and is administered into the tumor every 2 weeks for up to 8 cycles. Following the first dose, concurrent nivolumab infusion will be given with RP1 every 2 weeks, which is then followed by dosing every 4 weeks for up to 20 months.