Replimune Presents Primary Analysis Data from IGNYTE Clinical Trial of RP1 Combined with Nivolumab in Anti-PD1 Failed Melanoma at European Society for Medical Oncology (ESMO) Congress 2024

Rhea-AI Summary

Replimune Group (NASDAQ: REPL) presented primary analysis data from the IGNYTE clinical trial of RP1 combined with nivolumab in anti-PD1 failed melanoma at ESMO Congress 2024. The trial included 140 patients who received RP1 plus nivolumab after confirmed progression on anti-PD1 based therapy. Key results include:

- Overall response rate (ORR) of 33.6% by mRECIST and 32.9% by RECIST 1.1
- Complete response rate of 15% by mRECIST
- ORR of 27.7% in patients with prior anti-PD1 and anti-CTLA-4 treatment
- Median duration of response from treatment initiation was 27.6 months
- One-, two-, and three-year survival rates were 75.3%, 63.3%, and 54.8% respectively

The treatment was well-tolerated with mostly Grade 1-2 adverse events. Replimune plans to submit a BLA for RP1 in anti-PD1 failed melanoma in the second half of 2024.

Positive

• Overall response rate (ORR) of 33.6% by mRECIST and 32.9% by RECIST 1.1 criteria
• Complete response rate of 15% by mRECIST
• Median duration of response from treatment initiation was 27.6 months
• 85% of responses were ongoing more than a year from starting treatment
• One-, two-, and three-year survival rates were 75.3%, 63.3%, and 54.8% respectively
• RP1 combined with nivolumab was well-tolerated with mostly Grade 1-2 adverse events
• Planned BLA submission for RP1 in anti-PD1 failed melanoma in 2H 2024

Negative

• 12.8% of patients experienced Grade 3-4 adverse events
• Five patients experienced Grade 4 adverse events

Oncology Doctor

The IGNYTE clinical trial results for RP1 combined with nivolumab in anti-PD1 failed melanoma are promising. The 33.6% overall response rate and 15% complete response rate are clinically significant for this difficult-to-treat population. Notably, the 21.6-month median duration of response and 85% of responses ongoing after a year indicate durable efficacy. The 54.8% three-year survival rate is encouraging, considering these patients had progressed on prior therapies. The similar response rates in injected and non-injected lesions suggest a systemic immune effect, which is important for addressing metastatic disease. The safety profile appears manageable, with mostly low-grade adverse events. This combination could potentially offer a new option for patients with treatment choices after anti-PD1 failure.

Medical Research Analyst

The IGNYTE trial's primary analysis demonstrates RP1's potential as an oncolytic immunotherapy. Key points include:

• Efficacy across subgroups, including those with prior anti-CTLA-4 exposure (27.7% ORR) and primary anti-PD1 resistance (35.9% ORR)
• Durable responses with a 27.6-month median duration from treatment initiation
• Promising survival rates: 75.3%, 63.3% and 54.8% at 1, 2 and 3 years respectively

The similar response in injected and non-injected lesions supports RP1's mechanism of action in generating systemic anti-tumor immunity. The tolerability profile, with mainly Grade 1-2 events, is favorable for an immunotherapy combination. These results position RP1 plus nivolumab as a potential advancement in treating anti-PD1 refractory melanoma, addressing an unmet medical need.

Financial Analyst

Replimune's IGNYTE trial results are positive for the company's financial outlook. The data supports their planned BLA submission in H2 2024, potentially leading to market entry in a valuable indication. Key financial implications:

• Addressing the anti-PD1 failed melanoma market could provide significant revenue opportunities
• Durable responses may translate to extended treatment duration and recurring revenue
• The favorable safety profile could support broader adoption if approved
• Positive results in this trial may increase investor confidence in Replimune's pipeline

However, investors should note that regulatory approval is not guaranteed and commercialization challenges may arise in a competitive oncology market. The company's ability to execute on the BLA submission and potential launch will be crucial. Overall, these results strengthen Replimune's position in the oncolytic immunotherapy space and may positively impact its valuation.

Data from the IGNYTE primary analysis shows clinically meaningful activity across all subgroups, including those who had received prior anti-PD1 and anti-CTLA-4 or had primary resistance to anti-PD1

Injected and non-injected lesions responded with similar frequency, depth, duration and kinetics

WOBURN, Mass., Sept. 15, 2024 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, today announced that data from the primary analysis of the IGNYTE clinical trial of RP1 combined with nivolumab were presented by Caroline Robert, M.D., Ph.D. of Gustave Roussy as a late breaking abstract during an oral session at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona.

“We are excited to share the full IGNYTE primary analysis data which clearly shows clinically meaningful and durable systemic anti-tumor activity across the enrolled population, with responses in both injected and non-injected tumors, including visceral lesions,” said Kostas Xynos, MD, PhD, MBA, Chief Medical Officer of Replimune. “These positive data will form the basis of our upcoming BLA submission for RP1 in anti-PD1 failed melanoma in the 2H 2024, which is an important step forward as we continue to progress RP1 plus nivolumab as a potential new option in a setting with only limited treatments currently available.”

The anti-PD1 failed melanoma cohort from the IGNYTE clinical trial included 140 patients who received RP1 plus nivolumab after confirmed progression while being treated for at least 8 weeks with anti-PD1 based therapy (+/- anti-CTLA-4). The primary analysis by blinded independent central review was triggered once all patients had been followed for at least 12 months. Because of requirements that patients must have confirmed progressive disease on an immediate anti-PD1-based therapy, which is the current first line standard of care, most of the patients enrolled had 1 (45.7%) or 2 (18.6%) lines of prior therapies.

Results from the IGNYTE clinical trial presented at ESMO show:

• The overall response rate (ORR) was 33.6% by modified RECIST (mRECIST) 1.1 criteria, the primary endpoint as defined in the protocol, and 32.9% by RECIST 1.1 criteria, an additional sensitivity analysis requested by the FDA.
• The complete response rate by mRECIST was 15%.
• In patients who had prior anti-PD1 and anti-CTLA-4, the ORR was 27.7% and for those who had primary resistance to anti-PD1, the ORR was 35.9% by mRECIST.
• Median duration of response from response initiation was 21.6 months and media duration of response from treatment initiation was 27.6 months. At the time of the analysis, 85% of responses were ongoing more than a year from starting treatment.
• While median overall survival has not been reached, one-, two- and three-year survival rates were 75.3%, 63.3% and 54.8% respectively.
  

RP1 combined with nivolumab continues to be well-tolerated. Treatment-related adverse events associated with RP1 in combination with nivolumab were predominantly Grade 1-2 constitutional type events (> 5% of patients), including fatigue, chills, pyrexia, nausea, influenza-like illness, injection-site pain, diarrhea, vomiting, headache, pruritis, asthenia, arthralgia, myalgia, decreased appetite, and rash, with a low incidence (12.8% of patients) of Grade 3-4 events, which were predominantly Grade 3. Grade 4 events were one each of lipase increased, cytokine release syndrome, myocarditis, hepatic cytolysis and splenic rupture. There were no Grade 5 events.

The presentation is available on the Company website under Events and Presentations.

About RP1
RP1 (vusolimogene oderparepvec) 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 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, 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 Westwicke
339.970.2843
chris.brinzey@westwicke.com

Media Inquiries
Arleen Goldenberg
Replimune
917.548.1582
media@replimune.com

FAQ

What were the key results of Replimune's IGNYTE clinical trial for RP1 in melanoma?

The IGNYTE trial showed an overall response rate of 33.6% by mRECIST criteria, a complete response rate of 15%, and a median duration of response of 27.6 months from treatment initiation. The one-, two-, and three-year survival rates were 75.3%, 63.3%, and 54.8% respectively.

When does Replimune (REPL) plan to submit a BLA for RP1 in anti-PD1 failed melanoma?

Replimune plans to submit a Biologics License Application (BLA) for RP1 in anti-PD1 failed melanoma in the second half of 2024, based on the positive data from the IGNYTE clinical trial.

How well-tolerated was the RP1 plus nivolumab treatment in the IGNYTE trial?

RP1 combined with nivolumab was generally well-tolerated. Most adverse events were Grade 1-2, with 12.8% of patients experiencing Grade 3-4 events. There were five Grade 4 events and no Grade 5 events reported.

What was the response rate for patients with prior anti-PD1 and anti-CTLA-4 treatment in the REPL IGNYTE trial?

In patients who had prior anti-PD1 and anti-CTLA-4 treatment, the overall response rate (ORR) was 27.7% by mRECIST criteria in the IGNYTE trial for Replimune's RP1 plus nivolumab combination.