Replimune Presents New Analyses from the IGNYTE Study of RP1 plus Nivolumab in Anti-PD1 Failed Melanoma at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting

Rhea-AI Summary

Replimune (NASDAQ: REPL) presented new analyses from the IGNYTE clinical trial of RP1 plus nivolumab in anti-PD1 failed melanoma patients at ASCO 2025. The combination therapy showed an objective response rate of 32.9% and complete response rate of 15.0%, with landmark overall survival rates of 75.3%, 63.3%, and 54.8% at 1, 2, and 3 years respectively. Deep/visceral injections demonstrated higher response rates (40.9-42.9%) compared to superficial-only injections (29.8%). The treatment showed effectiveness in both injected (93.6% reduction) and non-injected lesions (79.0% reduction), with robust responses in liver and lung injections. Biosafety analysis confirmed RP1's safety profile, with minimal transmission risk and effectiveness of standard disinfection procedures.

Positive

• Strong objective response rate of 32.9% and complete response rate of 15.0% in anti-PD1 failed melanoma patients
• Impressive survival rates with 75.3%, 63.3%, and 54.8% at 1, 2, and 3 years respectively
• Higher response rates (40.9-42.9%) achieved with deep/visceral injections compared to superficial-only injections (29.8%)
• Strong reduction in both injected (93.6%) and non-injected (79.0%) lesions, demonstrating systemic effectiveness
• Favorable safety profile for liver and lung injections with manageable adverse events

Negative

• Median Overall Survival has not yet been reached, limiting long-term survival analysis
• Some risk of pneumothorax events with lung injections, though typically low grade
• Treatment requires direct tumor injection, which may limit accessibility for some patients

Insights

Oncology Clinical Trial Specialist

Replimune's RP1+nivolumab shows 32.9% response rate in anti-PD1 failed melanoma, with deep injections producing better outcomes than superficial ones.

Replimune has presented new analyses from their IGNYTE study combining RP1 (vusolimogene oderparepvec) with nivolumab in melanoma patients who failed prior anti-PD-1 therapy. The data reveal several clinically meaningful outcomes:

The combination achieved an objective response rate (ORR) of 32.9% using RECIST 1.1 criteria, with a complete response rate of 15.0% - impressive figures in this difficult-to-treat population. Landmark overall survival rates were 75.3% at 1 year, 63.3% at 2 years, and 54.8% at 3 years, with median overall survival not yet reached.

What's particularly interesting is how injection method impacts efficacy. Patients receiving deep/visceral injections (with or without superficial injections) showed numerically higher response rates (40.9%-42.9%) than those receiving only superficial injections (29.8%).

The data demonstrate robust systemic effects beyond just the directly treated tumors - 93.6% of injected lesions showed ≥30% reduction, while 79.0% of non-injected lesions also responded. Among non-injected visceral lesions in responding patients, 96.2% showed some reduction, with 65.4% reduced by ≥30% or more.

From a safety perspective, the deep/visceral injections, including directly into lung and liver, were generally well-tolerated with manageable adverse events. The biosafety analysis confirms standard disinfection procedures are sufficient for RP1 handling.

These results are meaningful for melanoma patients who have limited options after failing anti-PD-1 therapy and suggest RP1's potential to generate systemic immune responses against tumors throughout the body.

- RP1 plus nivolumab generated robust responses in both injected and non-injected lesions -

- Deep/visceral injections, including into the liver and lung, resulted in numerically higher rates of response compared to superficial injections only and were generally well tolerated -

WOBURN, Mass., June 01, 2025 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, today presented two posters highlighting data updates for RP1 (vusolimogene oderparepvec) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 30-June 3 in Chicago.

“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. “Additional data also presented at the meeting shows that RP1 can be handled safely with no additional biosafety protocols required confirming that standard disinfection procedures are sufficient for clean up.”

Key findings are outlined below.

Poster Presentation: Response analysis for injected and non-injected lesions and the safety and efficacy of superficial and deep RP1 injection in the registrational cohort of anti-PD-1-failed melanoma patients of the IGNYTE trial (Track: Melanoma/Skin Cancers; June 1, 2025, 9:00 am – 12:00 pm CDT; Location: Hall A, Board 20; Abstract: 9537)

• The poster included an analysis from the IGNYTE clinical trial of RP1 plus nivolumab in the cohort of anti-PD-1 failed melanoma patients (n=140). In the trial, the objective response rate (ORR) was 32.9% using RECIST 1.1. The complete response rate was 15.0% and landmark overall survival (OS) rates at 1, 2, and 3 years were 75.3%, 63.3%, and 54.8% respectively. Median OS has not been reached.
• Patients experienced numerically higher objective response rates after receiving deep injections (± superficial) compared with superficial injections only. Deep responses were observed in injected and non-injected lesions.
  • The ORR by injection type using RECIST 1.1 was 29.8% when only superficial lesions were injected, 42.9% for deep/visceral plus superficial injections injected, and 40.9% when only deep/visceral lesions were injected.
  • There was a ≥30% reduction in 93.6% (73/78) of injected lesions and 79.0% (94/119) of non-injected lesions. The kinetics of response were similar in injected vs non-injected lesions.
  • Of the non-injected visceral organ lesions in responding patients, 96.2% (50/52) showed reduction from baseline, with 65.4% reduced by ≥30%.
• RP1 injections directly into the lung and liver were generally well tolerated and resulted in few organ-specific adverse events that were easily managed.
  • Liver and lung injections had a tolerable safety profile.
  • No bleeding events were reported after liver injection.
  • Lung injections were associated with low rates of pneumothorax events, which were typically of low grade and manageable.
• Overall, these data support the safety and efficacy of deep/visceral injections and demonstrate the development of a robust systemic anti-tumor response following treatment with RP1 plus nivolumab.

Poster Presentation: Biosafety analysis from the skin cancer cohorts in the IGNYTE clinical trial of RP1 (Track: Melanoma/Skin Cancers; June 1, 2025, 9:00 am – 12:00 pm CDT; Location: Hall A, Board 17; Abstract: 9534)

• RP1 was assessed in various samples taken from patients. 
  • This demonstrated that RP1 DNA is primarily detected at the injection site, consistent with RP1 replication in the tumor, and much more rarely on dressings, in blood, on mucous membranes or in urine.
  • In all cases, live RP1 was only rarely if ever detected, demonstrating that while residual RP1 DNA may be present, this does not indicate the presence of live RP1 
  • There were no systemic herpetic infections in patients or reports of HSV-1 infections in contacts.
  • RP1 is completely neutralized using standard disinfectants within 30 seconds of contact, confirming that standard disinfection procedures are sufficient for RP1 clean-up.
• Collectively these data demonstrate that the likelihood of transmission of RP1 to patients’ contacts or into the external environment is minimal, with no transmission having been reported to date.

Both posters will be available on the Company website under Events and Presentations.

About RP1
RP1 is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response.

About RP2
RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP-R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.

About Replimune
Replimune Group, Inc., headquartered in Woburn, MA, was founded in 2015 with the mission to transform cancer treatment by pioneering the development of novel oncolytic immunotherapies. Replimune’s proprietary RPx platform is based on a potent HSV-1 backbone intended to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response. The RPx platform is designed to have a unique dual local and systemic activity consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor derived antigens and altering of the tumor microenvironment to ignite a strong and durable systemic response. The RPx product candidates are expected to be synergistic with most established and experimental cancer treatment modalities, leading to the versatility to be developed alone or combined with a variety of other treatment options. For more information, please visit www.replimune.com. 

Forward Looking Statements
This press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding the design and advancement of our clinical trials, the timing and sufficiency of our clinical trial outcomes to support potential approval of any of our product candidates, the regulatory review process and timing of potential product approval, our goals to develop and commercialize our product candidates, patient enrollments in our existing and planned clinical trials and the timing thereof, and other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Forward-looking statements are not promises or guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to generate positive clinical trial results for our product candidates, the costs and timing of operating our in-house manufacturing facility, the timing and scope of regulatory approvals, the availability of combination therapies needed to conduct our clinical trials, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, political and global macro factors including the impact of the coronavirus as a global pandemic and related public health issues and the Russian-Ukrainian and Israel-Hamas political and military conflicts, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q and other reports we file with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward-looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements.

Investor Inquiries
Chris Brinzey
ICR Healthcare
339.970.2843
chris.brinzey@icrhealthcare.com 

Media Inquiries
Arleen Goldenberg
Replimune
917.548.1582
media@replimune.com 

FAQ

What were the key results from Replimune's IGNYTE trial for RP1 in melanoma patients?

The trial showed a 32.9% objective response rate and 15.0% complete response rate, with survival rates of 75.3%, 63.3%, and 54.8% at 1, 2, and 3 years respectively. Deep/visceral injections showed higher response rates of 40.9-42.9% compared to superficial-only injections at 29.8%.

How effective is REPL's RP1 treatment in non-injected tumor lesions?

RP1 showed strong effectiveness in non-injected lesions with 79.0% showing reduction, and 96.2% of non-injected visceral organ lesions in responding patients showing reduction from baseline.

What is the safety profile of Replimune's RP1 injections in liver and lung?

Liver and lung injections were generally well tolerated with no bleeding events reported after liver injection. Lung injections had low rates of manageable pneumothorax events, typically of low grade.

Is there a risk of transmission with Replimune's RP1 treatment?

The biosafety analysis showed minimal transmission risk, with RP1 DNA primarily detected at injection sites. No systemic herpetic infections or HSV-1 infections in contacts were reported, and standard disinfection procedures effectively neutralize RP1.

What are the survival rates for REPL's RP1 plus nivolumab treatment in melanoma?

The landmark overall survival rates were 75.3% at 1 year, 63.3% at 2 years, and 54.8% at 3 years, with median overall survival not yet reached.