Replimune Presents Late-Breaking Abstract Featuring Data from IGNYTE Clinical Trial of RP1 Combined with Nivolumab in Anti-PD1 Failed Melanoma at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2024)
Replimune presented primary analysis data from the IGNYTE clinical trial evaluating RP1 combined with nivolumab in anti-PD1 failed melanoma patients at SITC 2024. The trial included 140 patients with a median follow-up of 15.4 months. Key results showed an overall response rate of 33.6% by mRECIST criteria, with a 15% complete response rate. The median duration of response was 21.6 months, with one-, two-, and three-year survival rates of 75.3%, 63.3%, and 54.8%, respectively. Biomarker data demonstrated increased CD8+ T cell and PD-L1 expression, indicating potential for generating anti-tumor immune responses. The treatment was well-tolerated with mostly Grade 1-2 adverse events.
Replimune ha presentato i dati dell'analisi primaria dello studio clinico IGNYTE, che valuta RP1 in combinazione con nivolumab nei pazienti affetti da melanoma che non hanno avuto successo con anti-PD1, durante il SITC 2024. Lo studio ha incluso 140 pazienti con un follow-up mediano di 15,4 mesi. I risultati chiave hanno mostrato un tasso di risposta complessivo del 33,6% secondo i criteri mRECIST, con un tasso di risposta completa del 15%. La durata mediana della risposta è stata di 21,6 mesi, con tassi di sopravvivenza a uno, due e tre anni rispettivamente del 75,3%, 63,3% e 54,8%. I dati sui biomarcatori hanno dimostrato un aumento delle cellule T CD8+ e dell'espressione di PD-L1, indicando un potenziale per generare risposte immunitarie anti-tumorali. Il trattamento è stato ben tollerato, con principalmente eventi avversi di grado 1-2.
Replimune presentó datos del análisis primario del ensayo clínico IGNYTE, que evalúa RP1 combinado con nivolumab en pacientes con melanoma que fracasaron con anti-PD1, durante el SITC 2024. El ensayo incluyó 140 pacientes con un seguimiento medio de 15,4 meses. Los resultados clave mostraron una tasa de respuesta general del 33,6% según los criterios mRECIST, con una tasa de respuesta completa del 15%. La duración media de la respuesta fue de 21,6 meses, con tasas de supervivencia a uno, dos y tres años de 75,3%, 63,3% y 54,8%, respectivamente. Los datos de biomarcadores demostraron un aumento en las células T CD8+ y en la expresión de PD-L1, lo que indica un potencial para generar respuestas inmunitarias anti-tumorales. El tratamiento se toleró bien, con principalmente eventos adversos de grado 1-2.
Replimune은 SITC 2024에서 anti-PD1 실패 멜라노마 환자에서 RP1과 니볼루맙을 결합한 IGNYTE 임상 시험의 주요 분석 데이터를 발표했습니다. 이 시험에는 140명의 환자가 포함되었으며, 중앙 추적 관찰 기간은 15.4개월이었습니다. 주요 결과는 mRECIST 기준에 따라 33.6%의 전체 반응률을 보였고, 15%의 완전 반응률을 기록했습니다. 반응의 중앙 지속 기간은 21.6개월이었으며, 1년, 2년 및 3년 생존율은 각각 75.3%, 63.3%, 54.8%였습니다. 바이오마커 데이터는 CD8+ T 세포와 PD-L1 발현의 증가를 보여주어 항종양 면역 반응을 생성할 잠재력을 나타냈습니다. 치료는 대부분 1-2등급의 부작용으로 잘 견딜 수 있었습니다.
Replimune a présenté les données d'analyse primaire de l'essai clinique IGNYTE évaluant le RP1 associé au nivolumab chez des patients atteints de mélanome ayant échoué aux anti-PD1 lors du SITC 2024. L'essai a inclus 140 patients avec un suivi médian de 15,4 mois. Les résultats clés ont montré un taux de réponse global de 33,6% selon les critères mRECIST, avec un taux de réponse complète de 15%. La durée médiane de la réponse était de 21,6 mois, avec des taux de survie à un, deux et trois ans respectivement de 75,3%, 63,3% et 54,8%. Les données sur les biomarqueurs ont démontré une augmentation des cellules T CD8+ et de l'expression de PD-L1, indiquant un potentiel pour générer des réponses immunitaires anti-tumorales. Le traitement a été bien toléré avec principalement des événements indésirables de grade 1-2.
Replimune stellte die primären Analyseergebnisse der IGNYTE-Studie vor, die RP1 in Kombination mit Nivolumab bei Melanompatienten untersucht, die mit Anti-PD1 versagt haben, auf dem SITC 2024. Die Studie umfasste 140 Patienten mit einer medianen Nachbeobachtungszeit von 15,4 Monaten. Die wichtigsten Ergebnisse zeigten eine Gesamtansprechrate von 33,6% nach mRECIST-Kriterien, mit einer 15% kompletten Ansprechrate. Die mediane Ansprechdauer betrug 21,6 Monate, mit Überlebensraten von 75,3%, 63,3% und 54,8% nach einem, zwei und drei Jahren. Biomarker-Daten zeigten eine erhöhte CD8+ T-Zell- und PD-L1-Expression, was auf ein Potenzial zur Erzeugung von antitumoralen Immunantworten hindeutet. Die Behandlung wurde gut vertragen, mit überwiegend unerwünschten Ereignissen der Grade 1-2.
- Overall response rate of 33.6% in anti-PD1 failed melanoma patients
- Complete response rate of 15%
- Median duration of response of 21.6 months
- Strong survival rates: 75.3% at 1 year, 63.3% at 2 years, 54.8% at 3 years
- 85% of both injected and non-injected lesions showed ≥30% size reduction
- Favorable safety profile with predominantly Grade 1-2 events
- Median PFS was only 3.7 months
- 12.8% of patients experienced Grade 3-4 adverse events
- Lower response rate (27.7%) in patients with prior anti-PD1 and anti-CTLA-4 therapy
Insights
The IGNYTE trial data shows compelling efficacy for RP1 plus nivolumab in anti-PD1 failed melanoma patients, with an overall response rate of 33.6% and a notable complete response rate of 15%. The durability of response is particularly impressive at 21.6 months, with strong survival rates (75.3%, 63.3% and 54.8% at years 1, 2 and 3). The biomarker data provides mechanistic validation, showing increased CD8+ T cell infiltration and PD-L1 expression - critical indicators of immune activation. The safety profile appears manageable, with mostly Grade 1-2 events and serious adverse events. This positions RP1 as a potentially significant treatment option for this difficult-to-treat patient population, where current options are
These clinical results significantly strengthen Replimune's market position in the $5.7 billion melanoma therapeutics market. The data is particularly valuable as it addresses a critical unmet need in anti-PD1 failed patients. The systemic response observed in both injected and non-injected lesions, including visceral sites, expands the potential patient population. With the IGNYTE-3 confirmatory phase 3 trial ongoing, positive results could lead to FDA approval and substantial market penetration. The robust durability of response and survival data could support premium pricing and favorable reimbursement decisions, potentially driving significant revenue growth.
Oral presentation highlighting IGNYTE primary analysis data shows anti-tumor activity across all subgroups with injected and non-injected lesions responding with similar frequency, depth, duration, and kinetics
Initial biomarker data shows increase in tumor CD8+ T cell and PD-L1 expression after dosing along with an increase in gene signatures associated with CD8+ T cells and inflammatory cytokines, highlighting the potential of RP1 plus nivolumab to generate a potent anti-tumor immune response
WOBURN, Mass., Nov. 09, 2024 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, today announced that the primary analysis data from the IGNYTE clinical trial, including initial biomarker analyses, was presented as a late-breaking abstract during an oral session at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2024) in Houston, Texas. In addition, data from the ARTACUS clinical trial evaluating RP1 monotherapy in solid organ transplant patients with advanced cutaneous malignancies was also shared in an encore poster presentation during the meeting.
“The initial biomarker analyses included in the SITC presentation which demonstrate increases in tumor CD8+ T cell infiltration and PD-L1 expression along with the induction of an immune inflammatory gene signature after treatment, further support the intended mechanism of RP1 in combination with nivolumab, including its ability to induce a systemic response after progression on prior anti-PD1 therapy,” said Kostas Xynos, MD, PhD, MBA, Chief Medical Officer of Replimune. “We believe that the systemic activity of RP1 and nivolumab is in particular demonstrated by the similar level of responses seen in both injected and non-injected lesions, including hard to treat visceral lesions, and by the durability of the responses seen.”
IGNYTE Clinical Trial Data at SITC
The IGNYTE clinical trial cohort in anti-PD-1 failed melanoma included 140 patients who received RP1 plus nivolumab after confirmed progression while being treated for at least 8 weeks with anti-PD-1 based therapy, with or without anti-CTLA-4. The primary analysis by blinded independent central review was triggered once all patients had been followed for at least 12 months. The median follow-up at the time of the primary analysis was 15.4 months (0.5-47.6 months).
Data from the IGNYTE trial presented at SITC 2024 show:
- One-third of patients experienced a confirmed response, with an overall response rate (ORR) of
33.6% by modified RECIST (mRECIST) v1.1 criteria, the primary endpoint in the trial protocol, and32.9% by RECIST v1.1 criteria, an additional analysis requested by the FDA. The complete response (CR) rate by mRECIST v1.1 was15% . In patients who had prior anti-PD1 and anti-CTLA-4, the ORR was27.7% and for those who had primary resistance to anti-PD1, the ORR was35.9% by mRECIST v1.1. - The median duration of response from response initiation was 21.6 months.
- Most injected and non-injected lesions (
85% ) in responders had a30% or greater reduction in size. RP1 plus nivolumab induced deep responses in non-injected lesions in visceral organs, including those distant from the injection site. - Median overall survival for the trial has not been reached, however, one-, two-, and three-year survival rates were
75.3% ,63.3% , and54.8% , respectively. 12-month progression free survival (PFS) was32.8% and median PFS was 3.7 months.
Initial biomarker data included in the SITC presentation show:
- Tumor inflammation signature (TIS) and nano string analysis revealed an increase in the expression of genes associated with CD8+ T cells and inflammatory cytokines. These markers highlight the potential of RP1 plus nivolumab to generate a potent anti-tumor immune response. TIS is an investigational use only assay consisting of 18 genes that assesses the presence of an adaptive immune response, and which is associated with responsiveness to anti-PD1 therapy1.
- Immunohistochemistry (IHC) images demonstrate that RP1 plus nivolumab may stimulate tumors to a more immune inflamed state, further highlighting the potential of RP1 plus nivolumab to reverse mechanisms of resistance to anti-PD1 therapy.
As previously reported, 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 (>
The presentation is available on the Company website under Events and Presentations.
The IGNYTE-3 confirmatory phase 3 trial evaluating RP1 plus nivolumab versus physician’s choice in patients with advanced melanoma who have progressed on anti-PD1 and anti-CTLA-4 or who are not candidates for anti-CTLA-4 therapy is currently recruiting. For additional information, visit https://replimune.com/clinical-trials/ignyte-3/.
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.
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FAQ
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