Replimune Group presented compelling new data from its IGNYTE clinical trial at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrating that deep tumor injections of its oncolytic immunotherapy RP1 combined with nivolumab produce enhanced response rates in patients with anti-PD-1 failed melanoma. The findings suggest that direct injection into visceral organs may optimize the therapeutic potential of this novel combination approach.
Enhanced Efficacy with Deep Injection Strategy
The IGNYTE trial analysis included 140 patients with anti-PD-1 failed melanoma treated with RP1 (vusolimogene oderparepvec) plus nivolumab. The combination achieved an objective response rate of 32.9% using RECIST 1.1 criteria, with a complete response rate of 15.0%. Landmark overall survival rates demonstrated durability, with 75.3%, 63.3%, and 54.8% of patients surviving at 1, 2, and 3 years respectively. Median overall survival has not been reached.
The data revealed a clear advantage for deep injection approaches. Patients receiving deep/visceral injections combined with superficial injections achieved a 42.9% objective response rate, compared to 29.8% for superficial injections alone. Deep/visceral injections exclusively yielded a 40.9% response rate, demonstrating the therapeutic value of targeting visceral lesions directly.
"The new analyses we presented from the IGNYTE clinical trial of RP1 plus nivolumab in anti-PD-1 failed melanoma confirms our belief in the systemic activity of the combination, and also shows robust responses in injected liver and lung lesions with an acceptable safety profile," said Kostas Xynos, M.D., Chief Medical Officer of Replimune.
Systemic Anti-Tumor Activity
The trial demonstrated robust systemic activity beyond injection sites. Among injected lesions, 93.6% (73/78) showed ≥30% reduction, while 79.0% (94/119) of non-injected lesions achieved similar reductions. The kinetics of response were comparable between injected and non-injected lesions, supporting the systemic mechanism of action.
Particularly notable was the response in non-injected visceral organ lesions among responding patients, where 96.2% (50/52) showed reduction from baseline, with 65.4% achieving ≥30% reduction. This systemic activity pattern supports RP1's mechanism of inducing immunogenic cell death and activating systemic anti-tumor immune responses.
Safety Profile of Visceral Injections
Direct injections into liver and lung demonstrated acceptable safety profiles with manageable organ-specific adverse events. No bleeding events were reported following liver injections, while lung injections were associated with low rates of pneumothorax events that were typically low grade and manageable.
Biosafety Confirmation
A separate biosafety analysis provided reassurance about RP1 handling and transmission risks. The study demonstrated that RP1 DNA is primarily detected at injection sites, consistent with tumor-specific replication, and rarely found on dressings, in blood, mucous membranes, or urine. Importantly, live RP1 was only rarely detected, and no systemic herpetic infections occurred in patients or contacts.
The analysis confirmed that RP1 is completely neutralized by standard disinfectants within 30 seconds, validating that standard disinfection procedures are sufficient for cleanup. No transmission events to patient contacts or the external environment have been reported.
Oncolytic Immunotherapy Platform
RP1 represents Replimune's lead product candidate based on a proprietary herpes simplex virus strain engineered with a fusogenic protein (GALV-GP-R-) and GM-CSF. This design aims to maximize tumor killing potency, enhance immunogenicity of tumor cell death, and activate systemic anti-tumor immune responses. The platform's dual local and systemic activity involves direct virus-mediated tumor killing while releasing tumor-derived antigens and modifying the tumor microenvironment to generate durable systemic responses.
