Tudriqev (vusolimogene oderparepvec-wtpg) / Replimune - LARVOL DELTA

Efficacy and safety of RP1 oncolytic immunotherapy (vusolimogene oderparepvec) in advanced melanoma: Real-world data from a single center (ESMO-IO 2025) - "Background RP1, an intratumoral oncolytic immunotherapy, in combination with nivolumab has shown promising efficacy in anti-PD1-failed, advanced melanoma, a population with limited safe and effective options. Median overall survival was not reached. Any-grade adverse events (AE) were observed in 81.8% pts (most common AE was chills); no grade ≥ 3 occurred.Conclusions RP1 +/- anti-PD-1 demonstrates meaningful clinical benefit and a manageable safety profile in pts with advanced melanoma and limited therapeutic options.Legal entity responsible for the study The authors."

Clinical • Metastases • Oncolytic virus • Real-world • Real-world evidence • Melanoma • Oncology • Solid Tumor

AN OPEN LABEL MULTICENTER PHASE 2 STUDY WITH SAFETY LEAD IN OF INTRATUMORAL VUSOLIMOGENE ODERPAREPVEC IN COMBINATION WITH PEMBROLIZUMAB IN PATIENTS WITH ANGIOSARCOMA (CTOS 2025) - P2 | "Standard treatments including paclitaxel or anthracycline based chemotherapies are associated with significant toxicities and tyrosine kinase inhibitors when used as single agents have limited response rates...In Phase 1/2 IGNYTE study trial cohort with anti-PD(L)-1 failed non melanomatous skin cancer including angiosarcoma patients, treated with intratumoral VO and IV nivolumab demonstrated an overall response rate of 33.3%. Patients aged ≥18 years with biopsy-proven cutaneous angiosarcoma that is either locally advanced and unresectable or metastatic, who have received and progressed on a first-line taxane- or anthracycline-based regimen and have received at least one prior immunotherapy-based regimen within 6 months prior to screening, are eligible for enrollment... N/A"

Clinical • Combination therapy • IO biomarker • P2 data • Angiosarcoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor

Abstract 600: Retreatment with RP1 in combination with nivolumab in patients with advanced anti-PD-1- failed melanoma (GlobeNewswire) - "Replimune presents...additional posters on RP1 at 40th Annual Meeting of the Society for the Immunotherapy of Cancer (SITC 2025)....Extended RP1 treatment beyond 8 doses was well tolerated providing clinical benefit in a majority of patients."

P2 data • Melanoma

Replimune Presents Late-Breaking Abstract…on RP1 at 40th Annual Meeting of the Society for the Immunotherapy of Cancer (SITC 2025) (GlobeNewswire) - "Treatment with RP1 plus nivolumab led to upregulation of gene signatures associated with responsiveness to PD-1 blockade. With additional follow-up (7 months), RP1 combined with nivolumab continues to demonstrate a clinically meaningful response rate (ORR: 33.6%) and durability (median duration of response: 24.8 months)....Median duration of response for PD-L1-negative patients was 24.8 months and for patients with primary resistance was 22.6 months."

Biomarker • Late-breaking abstract • P2 data • Cutaneous Melanoma

Abstract 611: RP1 plus nivolumab in patients with and without prior BRAF-directed therapy: A subgroup analysis of patients with anti-PD-1 failed BRAF-mutant melanoma from the IGNYTE clinical trial (GlobeNewswire) - "Replimune presents...additional posters on RP1 at 40th Annual Meeting of the Society for the Immunotherapy of Cancer (SITC 2025)....RP1 plus nivolumab demonstrated comparable efficacy in BRAF-mutant and BRAF–wild-type advanced melanoma. Greater activity was observed in BRAF-naïve patients - similar to findings from the SECOMBIT and DREAMseq trials."

P2 data • Melanoma

A publication for ARTACUS is planned for 2026. (GlobeNewswire)

P2 data • Cutaneous Melanoma • Squamous Cell Carcinoma

RP1 (vusolimogene oderparepvec) (GlobeNewswire) - "Upcoming Events: Society for Immunotherapy of Cancer (SITC) 2025 40th Annual Meeting being held November 5th to 9th, 2025."

Late-breaking abstract • P2 data • Melanoma

RP1 plus nivolumab in patients with and without prior BRAF-directed therapy: A subgroup analysis of patients with anti–PD-1–failed BRAF-mutant melanoma from the IGNYTE clinical trial (SITC 2025) - "This finding is consistent with literature showing that BRAF-directed therapy leads to cross-resistance to subsequent immunotherapy.Trial Registration ClinicalTrials.gov NCT03767348Ethics Approval The study was conducted in accordance with the ethical principles originating from the Declaration of Helsinki and was approved by the institutional review board/ethics committee at each participating site. Written informed consent was obtained from all patients prior to the conduct of any study-related procedures.Abstract 611 Table 1View inline•Open as popupEfficacy by prior BRAFi/MEKi treatment"

Clinical • IO biomarker • Melanoma • Oncology • Solid Tumor • BRAF

Retreatment with RP1 in combination with nivolumab in patients with advanced anti–PD-1–failed melanoma (SITC 2025) - "Additional clinical data from this collection of case reports will be presented.Trial Registration ClinicalTrials.gov NCT03767348Ethics Approval The study was conducted in accordance with the ethical principles originating from the Declaration of Helsinki and was approved by the institutional review board/ethics committee at each participating site. Written informed consent was obtained from all patients prior to the conduct of any study-related procedures."

Clinical • Combination therapy • Metastases • Melanoma • Oncology • Solid Tumor

Biomarker and updated clinical data for RP1 plus nivolumab in anti-PD-1-failed melanoma from the IGNYTE trial demonstrate reversal of mechanisms of resistance to immune checkpoint blockade (SITC 2025) - P2 | "Written informed consent was obtained from all patients prior to the conduct of any study-related procedures.Abstract 1327 Figure 1Request permissionsPharmacodynamic changes observed with RP1 plus nivolumab treatment following progression on anti-PD-1 therapy. Patients enrolled in the IGNYTE study experienced progression on anti-PD-1 therapy, making the observed pharmacodynamic changes (reversal of T-cell infiltration, increase in PD-L1 expression, increase in IFNγ signature, and increase in antigen presentation machinery) in tumors a likely contributor to RP1's mechanism of action.aPrevious line anti-PD-1-based therapies can include treatments such as ipilimumab, nivolumab, or pembrolizumab in combination with immunotherapies targeting proteins such as CTLA-4 or LAG-3.bDrawings of melanoma and sites of metastases are for illustrative purposes only and are meant to show extent of potential disease progression.cAssessed by blinded independent central..."

Biomarker • Checkpoint block • Checkpoint inhibition • Clinical data • IO biomarker • Late-breaking abstract • Tumor mutational burden • Melanoma • Oncology • Solid Tumor • CD68 • CD8 • CSF2 • GZMA • HLA-DRA • HLA-DRB1 • HLA-E • IFNG • LAG3 • PD-L1 • PRF1 • TMB • TRB

Response analysis for injected and non-injected lesions and of the safety and efficacy of superficial and deep/visceral RP1 injection in the registrational cohort of anti–PD-1–failed melanoma patients of the IGNYTE trial (JADPRO 2025) - "Prior anti-PD-1 therapy was nivolumab (53.6%), pembrolizumab (46.4%), or both (0%). Prior CTLA-4 inhibitor: 6.4% Prior BRAF/MEK inhibitor: 16.0% Prior chemotherapy: 32.0% Prior IL-2: 11.2% Prior T-VEC: 1.6% Prior other anti-cancer agents: 3.2% Sixty-one (48.8%) patients had prior anti-PD-1 monotherapy alone for advanced disease, 45.6% had anti-PD-1 + other agents, and 5.6% had received both therapies sequentially...Clinical activity of RP1 monotherapy was observed after deep/visceral injections or superficial injections only. Responses can be achieved by RP1 monotherapy and were reproducible in non-injected lesions."

Clinical • Cutaneous Melanoma • Eye Cancer • Hepatology • Melanoma • Mucosal Melanoma • Solid Tumor • Uveal Melanoma • IL2

IGNYTE: Unleashing the Combined Power of RP1 (VUSOLIMOGENE ODERPAREPVEC) and Nivolumab for Solid Tumors (ESMO 2025) - "Sponsored by Replimune Inc"

Oncology • Solid Tumor

The Evolution, Current Landscape, and Future Prospects of Oncolytic Virotherapy in Melanoma: Talimogene Laherparepvec and Beyond. (PubMed, Cells) - "We begin by describing early investigations using wild type viruses and then the development of sophisticated Herpes simplex virus 1 (HSV-1) variant constructs such as talimogene laherparepvec (T-VEC) and vusolimogene oderparepvec (Replimune-1, RP1), which incorporate deletions of viral genes and expression of human or synthetic transgenes to promote tumor selectivity, dendritic cell recruitment, antigen presentation, and stimulation of systemic anti-tumor immune responses. We review the status of clinical trials of oncolytic viruses in melanoma, highlight regulatory challenges, and describe important concepts and key remaining questions within the field. While T-VEC remains the only Food and Drug Administration (FDA)-approved oncolytic virus for melanoma treatment, ongoing research focusing on next-generation viral constructs and combination strategies aims to further improve clinical outcomes and expand the applicability of oncolytic virus therapy in melanoma."

IO biomarker • Journal • Review • Herpes Simplex • Melanoma • Oncology • Solid Tumor

Biosafety analysis from the skin cancer cohorts in the IGNYTE clinical trial of RP1 (JADPRO 2025) - "* **No live, replication-competent RP1 was detected in any patient sample** at or after the Day 1 post-dose follow-up time point. * The low levels of RP1 DNA shedding, the **lack of live virus detection** in clinical samples, and the demonstration that the virus is **easily inactivated by common disinfectants** all suggest a **favorable biosafety profile** for RP1."

Clinical • IO biomarker • Genetic Disorders • Herpes Simplex • Infectious Disease • Melanoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CSF2

Efficacy and safety of RP1 plus nivolumab in patients with advanced anti–PD-1-failed acral melanoma (ESMO 2025) - P2 | "Conclusions RP1 + nivo demonstrated deep and durable efficacy and was well tolerated in pts with advanced anti–PD-1–failed acral melanoma. RP1 + nivo represents a promising treatment approach for this rare, aggressive melanoma subtype."

Clinical • Metastases • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF • PD-L1

Efficacy and safety of RP1 + nivolumab (nivo) in patients with non-melanoma skin cancer (NMSC) (ESMO 2025) - P2 | "Table: 1661P Confirmed response by NMSC type BOR, n (%) MCC BCC Angiosarcoma CSCC PD-1 naïve CSCC PD-1 failed PD-1 naïve (n = 4) PD-1 failed (n = 19) PD-1 naïve (n = 3) PD-1 failed (n = 10) PD-1 naïve (n = 6) PD-1 failed (n = 8) LA (n = 5) Met (n = 11) Total (n = 16) LA (n = 8) Met (n = 25) Total (n = 33) CR 4 (100) 3 (15.8) 1 (33.3) 0 2 (33.3) 2 (25.0) 2 (40.0) 4 (36.4) 6 (37.5) 1 (12.5) 1 (4.0) 2 (6.1) PR 0 2 (10.5) 0 3 (30.0) 2 (33.3) 1 (12.5) 1 (20.0) 2 (18.2) 3 (18.8) 1 (12.5) 2 (8.0) 3 (9.1) ORR 4 (100) 5 (26.3) 1 (33.3) 3 (30.0) 4 (66.7) 3 (37.5) 3 (60.0) 6 (54.5) 9 (56.3) 2 (25.0) 3 (12.0) 5 (15.2) BOR, best overall response. Conclusions RP1 + nivo induced responses across multiple NMSC tumor types, including anti–PD-1–failed disease, and represents a promising treatment approach for pts with advanced skin cancers, including those with disease progression on prior anti–PD-1 therapy."

Clinical • Angiosarcoma • Basal Cell Carcinoma • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

The Next Step in Advanced Melanoma: The IGNYTE-3 Study with RP1 and Nivolumab (ESMO 2025) - "Sponsored by Replimune Inc"

Metastases • Melanoma • Oncology • Solid Tumor

The Combination of RP1 Plus Nivolumab for Non-Melanoma Skin Cancer (ESMO 2025) - "Sponsored by Replimune Inc"

Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Replimune…announced that the U.S. Food and Drug Administration (FDA) has accepted the resubmission of the Biologics License Application (BLA) for RP1 in combination with nivolumab for the treatment of advanced melanoma in patients who progress on an anti-PD-1 containing regimen (GlobeNewswire) - "The PDUFA date set by the FDA is April 10, 2026 based on a Class II resubmission timeline....The FDA indicated this resubmission is considered to be a complete response to the complete response letter received in July 2025."

FDA filing • PDUFA • Melanoma

Replimune Highlights Acral Melanoma Data for RP1 plus Nivolumab at the ESMO Congress 2025 (GlobeNewswire) - "The analysis of acral melanoma patients from the IGNYTE clinical trial showed treatment with RP1 combined with nivolumab resulted in an objective response rate of 44% (8/18) with a median duration of response of 11.9 months (3.9, not reached). The safety profile was favorable with generally transient grade 1 and 2 treatment related adverse events."

dMMR • MSI-H • P2 data • Cutaneous Melanoma • Microsatellite Instability

Replimune Provides Update Following Type A Meeting with FDA (GlobeNewswire) - "Replimune...completed a Type A meeting with the U.S. Food and Drug Administration (FDA) on September 16th to discuss the complete response letter (CRL) for the Company’s Biologics License Application (BLA) for RP1 in combination with nivolumab for the treatment of advanced melanoma. The company is evaluating the feedback from the FDA provided during the meeting to determine next steps. At this time, a path forward under the accelerated approval pathway has not been determined."

FDA event • Melanoma

Replimune (REPL) Faces Investor Lawsuit After FDA Blocks Cancer Drug Approval - Hagens Berman (GlobeNewswire) - "A newly filed securities class action accuses the biotech firm and its leadership of concealing critical risks tied to its flagship cancer therapy, RP1, and overstating the strength of clinical trial data used to support its FDA application."

Corporate lawsuit • Melanoma

A Phase 3 randomized, controlled, multicenter study of vusolimogene oderparepvec in combination with nivolumab compared to treatment of physician's choice in patients with advanced melanoma who has progressed on anti-PD-1 and anti-CTLA-4 therapy (IGNYTE-3) (ADO 2025) - No abstract available

Clinical • Combination therapy • Metastases • P3 data • Melanoma • Solid Tumor

Replimune Group, Inc…announced that a Type A meeting with the U.S. Food and Drug Administration (FDA) has been scheduled to discuss the complete response letter (CRL) for the Company’s Biologics License Application (BLA) for RP1 in combination with nivolumab for the treatment of advanced melanoma. (GlobeNewswire)

FDA event • Melanoma

Replimune Reports Fiscal First Quarter 2026 Financial Results and Provides Corporate Update (The Manila Times) - "Program Highlights & MilestonesRP1 (vusolimogene oderparepvec): The global Phase 3 trial, IGNYTE-3 assessing RP1 in combination with nivolumab is ongoing. The trial is expected to enroll approximately 400 patients across 100 sites globally and is assessing RP1 in combination with nivolumab in patients with advanced melanoma who have progressed on anti-PD-1 and anti-CTLA-4 therapies or are ineligible for anti-CTLA-4 treatment....Following the CRL, the Company anticipates discussing the design of this trial with the FDA."

Trial status • Melanoma