FDA Accepts BLA for RP1 With Nivolumab in Advanced Melanoma

Extreme close-up of a melanoma: © mavis - stock.adobe.com

• The FDA accepted the biologics license application (BLA) for RP1 (vusolimogene oderparepvec) in combination with nivolumab (Opdivo) for the treatment of patients with advanced melanoma.
• Primary analysis data from the IGNYTE trial (NCT03767348) support this BLA.
• The BLA was granted priority review and a Prescription Drug User Fee Act (PDUFA) target action date of July 22, 2025, has been set.

The FDA accepted the BLA for the combination of RP1 with nivolumab for the treatment of patients with advanced melanoma, and the BLA was granted priority review.¹

With this, a PDUFA target action date of July 22, 2025, has been set.

“There are limited treatment options and a significant unmet need for patients with advanced melanoma who previously received an anti–PD-1 containing regimen,” said Sushil Patel, PhD, chief executive officer, Replimune, in a press release. “The BLA acceptance is an important milestone for Replimune, and we look forward to working closely with the FDA on the review of our application.”

Findings from the primary analysis of the IGNYTE trial support this BLA.² Among the 140 patients with advanced melanoma included in the study, the confirmed overall response rate (ORR) by independent central review (ICR) was 33.6% (n = 47; 95% CI, 25.8%-42.0%) with a 15.0% (n = 21) complete response rate by modified RECIST 1.1 (mRECIST 1.1) criteria. The ORR was 32.9% (n = 46; 95% CI, 25.2%-41.3%) by RECIST 1.1. The median duration of response (DOR) by mRECIST 1.1 was 21.6 months (95% CI, 14.5-not reached [NR]).

In patients with primary anti–PD-1 resistance, the ORR was 34.4%, and in patients who received prior anti–PD-1 with anti–CTLA-4, this rate was 26.2%. In years 1 and 2, the landmark OS rates were 75.3% (95% CI, 66.9-81.9) and 63.3% (95% CI, 53.6-71.5), and the 3-year survival rate was 54.8%. The median OS was not reached.

For safety, most treatment-related adverse events (TRAEs) were grade 1 or 2. The grade 3 or higher TRAE rate was 12.8%. TRAEs of all grades were seen in 89.4% of patients and grade 3 or 4 TRAEs were seen in 12.8%. The most common all-grade TRAEs included fatigue (32.6%), chills (31.9%), pyrexia (30.5%), nausea (22.0%), and influenza-like illness (17.7%). TRAEs deemed grades 3 or 4 included fatigue, diarrhea, asthenia, arthralgia, decreased appetite (0.7% each). Additionally, no grade 5 events were reported and there were no RP1-related deaths.

The FDA informed Replimune that they are not currently planning to hold an advisory committee meeting in relation to this application. At this time, they have not identified any potential review issues.

The confirmatory phase 3 IGNYTE-3 trial (NCT06264180) is currently enrolling patients with advanced melanoma who have progressed on anti-PD1 and anti–CTLA-4 therapy, or who are not candidates for anti–CTLA-4 treatment. Patients in the study are receiving RP1 in combination with nivolumab. The primary end point of the trial is OS, and secondary end points include PFS and ORR.³

REFERENCES:

1. Replimune announces biologics license application acceptance and priority review for RP1 for the treatment of advanced melanoma. News release. Replimune Group, Inc. January 21, 2025. Accessed January 21, 2025. https://tinyurl.com/b7rewhbt

2. Robert C, Milhem MM, Sacco JJ, et al. Primary efficacy, safety, and survival data from the registration-intended cohort of patients with anti-PD-1-failed melanoma from the IGNYTE clinical trial with RP1 combined with nivolumab. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA46. VO and nivolumab vs physician’s choice in advanced melanoma that progressed on anti-PD-1 & anti-ctla-4 drugs (IGNYTE-3). ClinicalTrials.gov. Updated November 20, 2024. Accessed January 21, 2025. https://clinicaltrials.gov/study/NCT06264180