This study is designed to establish the foundation for a new therapy for neurofibromatosis Type I (NF1)-related cutaneous neurofibromas (cNFs) by assessing the feasibility and efficacy of IMLYGIC in adults with NF1 and cNFs who desire local treatment of their cNF due to disfigurement, progression, pain, itching or other concerns. This is a single institutional Phase 1 study with a safety run-in to assess the feasibility and efficacy of IMLYGIC monotherapy in NF1 patients with cNFs. Each 28-day treatment cycle will be defined as intralesional administration of IMLYGIC administered on day 1 and 21 of Cycle 1 and days 7 and 21 for Cycles 2-4 for up to 4 cycles.

Start Date01 Feb 2026

Sponsor / Collaborator

The Johns Hopkins University

[+2]

NCT06660810

/ Active, not recruitingPhase 2IIT

Neoadjuvant Intralesional Injection of Talimogene Laherparepvec With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas

The proposed study is designed to treat locally advanced soft tissue sarcoma (STS) subtypes with neoadjuvant talimogene laherparepvec (TVEC) and preoperative external beam radiation therapy (EBRT).

Start Date03 Mar 2025

Sponsor / Collaborator

University of Iowa

[+1]

NCT04065152

/ RecruitingPhase 2IIT

Phase II Multicenter Study of Talimogene Laherparepvec in Classic or Endemic Kaposi Sarcoma - KAPVEC

Kaposi Sarcoma (KS) is a lymphangioproliferation associated with human herpes virus 8 (HHV8) promoted by immunosuppression. HIV-related KS and iatrogenic posttransplantation KS are treated by immune restoration, in association with local or systemic therapies as chemotherapies if required. Conversely in classic and endemic KS, the underlying relative immunosuppression cannot be directly targeted. Treatment is poorly codified, mostly based on surgery or radiotherapy for localized KS. Most aggressive forms with visceral involvement are treated with chemotherapies or interferon, which give at best 30-60% of transient responses and may not be well tolerated in elderly patients.
Talimogene laherparepvec is the first oncolytic immunotherapy approved by the FDA, in metastatic or unresectable melanoma with injectable nodal or cutaneous lesions. It is designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity.
In Merkel cell carcinoma (MCC), another virus-induced tumor, treatment with PD-1/PD-L1 axis inhibitors have proven efficacy, thus providing a proof of principle that immunotherapy could be effective in virus-induced tumors. Two cases of metastatic MCC successfully treated with talimogene laherparepvec were recently reported, suggesting that talimogene laherparepvec may also be an effective therapeutic option. Considering the high immunogenicity of viral epitopes in KS tumors, the role of the immune evasion in the development of KS, and the cutaneous manifestations (>90% of patients) that can be easily injected, classic and endemic KS is a good tumor model to be targeted with talimogene laherparepvec. The main objective is to assess whether talimogene laherparepvec is clinically inactive (partial+complete response probability π0<10%) or truly active (partial+complete response probability π1>40%) in classic and endemic Kaposi sarcoma.

Start Date01 Jan 2021

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

100 Clinical Results associated with Talimogene laherparepvec

100 Translational Medicine associated with Talimogene laherparepvec

100 Patents (Medical) associated with Talimogene laherparepvec

391

Literatures (Medical) associated with Talimogene laherparepvec

01 Mar 2026·Genes & Diseases

Engineering HSV-1 for oncolytic therapy: From molecular entry mechanisms to retargeting strategies

Review

Author: Gao, Yingzheng ; Tao, Juan ; Wang, Jixuan ; Huang, Xinwei ; Jiang, Dewei ; Nie, Zuqing ; Yan, Jingyuan ; Zou, Yufang ; Wang, Pengfei

Oncolytic viruses (OVs) represent a cutting-edge approach to cancer immunotherapy, characterized by their ability to selectively infect and eliminate tumor cells while sparing healthy tissues. Among the diverse OVs, type 1 herpes simplex virus (HSV-1) stands out due to its robust oncolytic activity, genetic malleability, broad cell tropism, and well-documented clinical safety. Advances in genetic engineering have further amplified the therapeutic efficacy of HSV-1 by enhancing tumor specificity, replication efficiency, and immunogenicity. Clinically significant HSV-1-based oncolytic viruses, such as T-VEC and G47Δ, have gained regulatory approvals for treating melanoma and malignant glioma, respectively, highlighting their transformative potential in cancer therapy. The attenuation strategies employed in most oncolytic HSV-1 (oHSV-1) strains, while ensuring safety, often reduce viral replication and cytotoxicity. To address this limitation, retargeting strategies focusing on HSV-1 glycoproteins (gD, gH/gL, and gB) have been developed. These modifications aim to abolish canonical receptor interactions and achieve tumor-specific targeting through ligand-receptor binding. Recent breakthroughs in understanding HSV entry mechanisms have enabled the creation of fully retargeted HSV vectors with enhanced specificity and efficacy. This review explores the molecular mechanisms underlying HSV glycoprotein-mediated cell entry, examines recent advances in receptor-retargeted oHSV-1 engineering, and discusses the challenges and future directions in the development of oncolytic HSV-based therapies.

01 Mar 2026·DRUG RESISTANCE UPDATES

Overcoming resistance in oncolytic virotherapy: Nano-engineered solutions for systemic delivery and efficacy boost

Review

Author: Wang, Geyuan ; Fan, Rangrang ; Zou, Bingwen ; Tong, Aiping ; Guo, Gang ; Wang, Xiaoxiao ; Zhou, Liangxue ; Han, Bo

Oncolytic virotherapy (OVT) has emerged as a transformative cancer treatment, leveraging tumor-selective viral replication to induce direct oncolysis and stimulate systemic antitumor immunity. Despite clinical advancements, including the FDA-approved T-VEC and subsequent agents, significant challenges remain, particularly in systemic delivery and therapeutic efficacy optimization. Intratumoral administration is largely restricted to superficial lesions, whereas intravenous delivery is hindered by rapid immune clearance due to viral antigen exposure. Additionally, insufficient antitumor efficacy presents another major hurdle, driving the growing trend of combinatorial therapies that exert synergistic effects. To overcome these barriers, nanotechnology-driven strategies, encompassing masking, targeting, and arming approaches, are revolutionizing OVT by enhancing viral stealth, improving tumor specificity, and amplifying therapeutic efficacy. Furthermore, considering biosafety concerns associated with live viral therapeutics, alternative functional nanoparticles that mimic oncolytic virus activity have been developed. These include synthetic oncolytic viruses, oncolytic peptides and polymers empowered by nanotechnology, and structurally mimetic nanoparticles. These engineered nanosystems have demonstrated potent oncolytic activity, positioning them as promising alternatives to traditional OVs while retaining their tumor-lytic functions. In this review, we explore how nanotechnology is redefining oncolytic virotherapy, focusing on masking, targeting, and arming nano-strategies. Additionally, we comprehensively examine the potential of nanoparticles to mimic and even replace oncolytic viruses, offering new avenues for enhanced cancer treatment.

01 Mar 2026·Molecular therapy. Oncology

Safety and feasibility of talimogene laherparepvec in peritoneal surface malignancies: Results from the TEMPO trial

Article

Author: Lowe, Melissa ; Mettu, Niharika ; Moyer, Ashley ; Stewart, John H ; MacLaughlan, Shannon Diane ; Bolch, Emily ; Blazer, Dan G ; Levine, Edward A ; Niedzwiecki, Donna ; Moaven, Omeed ; Strickler, John H

Peritoneal surface malignancies (PSMs) remain a therapeutic challenge, particularly in patients with unresectable disease who cannot benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies (TEMPO) trial (NCT03663712) is the first phase 1, multicenter, open-label study to evaluate intraperitoneal (i.p.) administration of talimogene laherparepvec (T-VEC), an FDA-approved oncolytic virus, in this setting. Nineteen patients with unresectable PSMs from appendiceal, ovarian, small bowel, and peritoneal carcinomas were enrolled; 18 received treatment across three escalating dose cohorts (4 × 10⁶-4×10⁸ PFU). The primary endpoint was safety and tolerability, with secondary endpoints assessing viral kinetics and shedding, and an exploratory efficacy endpoint. T-VEC demonstrated a manageable safety profile, with gastrointestinal and systemic toxicities more frequent at higher doses but no dose-limiting toxicities; one case of grade 3 neutropenia was observed. Herpes simplex virus 1 (HSV-1) DNA exhibited a dose-dependent persistence pattern, peaking later in higher dose cohorts, while plasma and urine remained consistently negative, supporting biosafety. Clinically, one complete response and ten cases of stable disease (4-19 months) were observed, while six patients experienced progression. These findings establish the safety and feasibility of i.p. T-VEC for unresectable PSMs, demonstrate localized viral replication without systemic dissemination, and suggest preliminary signals of clinical activity warranting further investigation in larger, more diverse cohorts.

News (Medical) associated with Talimogene laherparepvec

04 Feb 2026

·www.prnewswire.com

Oncolytic Virus Clinical Trial Landscape Gains Momentum: 100+ Companies Lead the Charge in Pioneering New Treatments | DelveInsight

The oncolytic virus therapy landscape has expanded steadily over the past decade, with over 100 companies worldwide pursuing clinical or preclinical programs. A few leaders, such as Candel Therapeutics, Binhui Biopharmaceutical, Oncolytics Biotech, EpicentRx, Hangzhou Converd, and others, anchor the mid and late-stage pipeline. LAS VEGAS, Feb. 4, 2026 /PRNewswire/ -- DelveInsight's Oncolytic Virus Competitive Landscape 2026 report provides comprehensive global coverage of pipeline oncolytic virus therapies across various stages of clinical development. The report offers an in-depth analysis of key trends, emerging therapies, and the competitive landscape, highlighting the strategies of major pharmaceutical companies to advance their pipelines and capitalize on future growth opportunities. In addition, it provides critical insights into clinical trial benchmarking, partnering and licensing, and regulatory pathways with the FDA and EMA, enabling stakeholders to make informed decisions and optimize development strategies in the oncolytic virus domain. Oncolytic Virus Clinical Trial Analysis Summary DelveInsight's oncolytic virus pipeline report highlights a robust landscape, with 100+ active players developing 110+ oncolytic virus drugs. Key oncolytic virus companies such as Oncolytics Biotech, SillaJen, Candel Therapeutics, Binhui Biopharmaceutical, Oryx GmbH, Oncolys Biopharma, EpicentRx, Theriva Biologics, Lokon Pharma, DNAtrix, Surv BioPharma Inc., Treovir, Immvira Pharma, Virogin Biotech, OrienGene Biotechnology, Apices Soluciones, Vyriad, Transgene, BioEclipse Therapeutics, Imugene, CG Oncology, Istari Oncology, Akamis Bio, Elicera Therapeutics, and others are evaluating new oncolytic virus drugs to improve the treatment landscape. Promising pipeline oncolytic virus therapies, such as Pelareorep, Pexa-Vec, CAN-2409, BS001, ParvOryx, Telomelysin, AdAPT-001, VCN-01, LOAd 703, DNX-2401, Surv.m-CRA-1, G207, MVR-T3011, VG161, OrienX010, AloCelyvir, Voyager-V1, TG6002, CRX-100, CF33-hNIS, CG0070, PVS-RIPO, NG-350A, ELC-201, and others, are in different phases of oncolytic virus clinical trials. Request a sample and discover the recent advances in oncolytic virus drugs @ Key Factors Driving the Oncolytic Virus Therapy Market Growing Cancer Incidence: The global rise in cancer prevalence, especially in hard-to-treat solid tumors, has intensified demand for novel, effective treatment modalities. Conventional therapies such as chemotherapy and radiation often have significant side effects and limited long-term efficacy, motivating the adoption of immunotherapeutic alternatives like oncolytic virus therapies. Increasing Understanding of Cancer Biology: Growing knowledge of cancer biology has enabled the development of oncolytic virus therapies that selectively target and destroy cancer cells while sparing healthy cells. Advancements in Viral Engineering: These advances are enabling more precise, targeted oncolytic virus therapies, significantly expanding the global oncolytic virus therapy market. Rising Adoption of Personalized Medicine: Oncolytic virus therapies align closely with personalized treatment approaches by enabling tailored viral constructs and immunomodulatory payloads based on tumor genomics. What is Oncolytic Virus Therapy? Oncolytic virus therapy is an innovative form of cancer treatment that uses genetically engineered or naturally occurring viruses to selectively infect and destroy cancer cells. These viruses replicate inside tumor cells, causing them to burst while leaving healthy cells largely unharmed. As the cancer cells break apart, they release tumor antigens that help activate the body's immune system, enhancing its ability to recognize and attack remaining cancer cells. This dual action, direct tumor destruction and immune stimulation, makes oncolytic virus therapy a promising approach in modern oncology, often used alongside other treatments such as immunotherapy or chemotherapy. Applications of Oncolytic Virus Therapy Oncolytic virus (OV) cancer therapies can be used for both diagnosis and treatment of cancer. OVs can function as cancer vaccines by boosting tumor-specific T-cell responses. Oncolytic viruses can be engineered with immunostimulatory molecules to enhance immune activation. OVs show strong synergy when combined with other immunotherapies, such as checkpoint inhibitors. Oncolytic Viruses in Combination with Chemotherapy Chemotherapy works systemically, unlike surgical resection or radiotherapy. It remains essential for treating patients with disseminated (widespread) cancer. Because chemotherapy is systemic, it is often combined with oncolytic viruses (OVs), which typically require localized delivery to achieve a strong antitumor effect. Systemically administered OVs have shown limited therapeutic benefit in several clinical trials. Delivering OVs effectively to metastatic sites remains a major challenge. Therefore, using chemotherapy as a systemic adjuvant to localized OV therapy is of significant clinical interest and is currently being actively investigated. Oncolytic Virus Market Analysis: Drug Profile IMLYGIC: Amgen IMLYGIC (talimogene laherparepvec), developed by Amgen, is a first-of-its-kind oncolytic viral therapy for melanoma that cannot be surgically removed. It combines direct tumors destruction with immune system stimulation. The therapy is based on a genetically engineered herpesvirus engineered to preferentially infect and destroy cancer cells, releasing GM-CSF to trigger a broader anti-tumor immune response. In the Phase III OPTiM trial, IMLYGIC produced durable responses in about 16% of patients, compared with 2% with GM-CSF alone, and overall responses in roughly 26%. Patients at earlier disease stages achieved better outcomes, with some achieving long-term control. The treatment is usually well tolerated, with most adverse effects being mild and resembling flu symptoms. Although its independent effect on survival and deep organ metastases is modest, its value is most evident when combined with checkpoint inhibitors. Early data show response rates approaching 56%, and ongoing studies aim to further define these synergistic benefits. As the first FDA-approved oncolytic virus in the West, IMLYGIC has validated the broader concept of viral immunotherapy and is now being explored as a component of combination immuno-oncology approaches. Oncorine: Shanghai Sunway Biotech Oncorine, also known as H101, is a genetically engineered adenovirus with an E1B gene deletion developed by Shanghai Sunway Biotech in China. It is administered alongside chemotherapy to treat nasopharyngeal carcinoma and head and neck cancers. Its approval and effective clinical use have significantly advanced oncolytic virus–based cancer immunotherapy. Marketed as Recombinant Human Adenovirus Type 5 Injection, Oncorine became the first oncolytic virus approved for cancer treatment by the Chinese State Food and Drug Administration (CFDA) in November 2005. Since its introduction, it has demonstrated a favorable safety profile and notable antitumor activity across various cancers and malignant pleural effusions. Exploratory clinical studies have also evaluated Oncorine for treating liver cancers, pancreatic cancer, cervical cancer, malignant melanoma, and metastatic liver tumors. Find out more about oncolytic virus cancer drugs @ Oncolytic Virus Analysis A snapshot of the Pipeline Oncolytic Virus Drugs mentioned in the report: Learn more about the emerging oncolytic virus therapies @ Oncolytic Virus Clinical Trials Recent Developments in Oncolytic Virus Treatment Space In November 2025, Imugene Ltd and JW Therapeutics announced a co-development collaboration to evaluate the combination of Imugene's oncolytic virus CF33-CD19 (onCARlytics) and JW's Carteyva®, a CD19-directed autologous CAR-T cell therapy, for patients with advanced solid tumors. This collaboration includes preclinical in vitro and in vivo studies, followed by a Phase I investigator-initiated trial to be conducted exclusively in China at premier CAR-T clinical centers. The approach utilizes Imugene's CF33-CD19 virus to induce CD19 expression on tumor cells, rendering them susceptible to targeting by CD19 CAR-T therapies, a transformative "mark and kill" strategy. In July 2025, Calidi Biotherapeutics, Inc., a clinical-stage biotechnology company pioneering the development of targeted therapies with the potential to deliver genetic medicines to distal sites of disease, announced that it received Fast Track designation from the U.S. Food and Drug Administration (FDA) for CLD-201 (SuperNova), the company's allogeneic adipose stem-cell loaded oncolytic virus for the treatment of soft tissue sarcoma. In June 2025, Oncolytics Biotech presented a poster demonstrating the role of pelareorep in activating anti-tumor immunity in PDAC. In May 2025, Candel Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) had granted Regenerative Medicine Advanced Therapy (RMAT) designation to CAN-2409 (aglatimagene besadenovec), the Company's biological immunotherapy lead candidate, for the treatment of newly diagnosed localized prostate cancer in patients with intermediate-to-high-risk disease. CAN-2409 was also previously granted FDA Fast Track designation for the same indication. In May 2025, Elicera Therapeutics AB announced that it had entered into a Material Transfer Agreement (MTA) with University Hospital Tübingen in Germany. Under the agreement, the company's oncolytic virus candidates ELC-100 and ELC-201 will be included in tests aimed at developing a new type of companion diagnostic to predict the potential success of a novel neuroendocrine neoplasm (NEN) therapy, immuno-virotherapy. In April 2025, Hangzhou ConVerd Co., Ltd. announced that the first Phase IIa clinical study of hV01, ConVerd's first oncolytic vaccinia virus product, had successfully completed first patient dosing, with the subject in good condition. This phase IIa clinical study investigates the administration of a single dose of recombinant human IL-21 oncolytic poxvirus injection (hV01) per cycle for the treatment of patients diagnosed with advanced sarcoma and cervical cancer. It is important to note that the indication is for advanced sarcoma and recurrent or metastatic cervical cancer for which there is no standard of care available at this stage of the treatment process, or where standard of care has failed. Scope of the Oncolytic Virus Pipeline Report Coverage: Global Key Oncolytic Virus Companies: Oncolytics Biotech, SillaJen, Candel Therapeutics, Binhui Biopharmaceutical, Oryx GmbH, Oncolys Biopharma, EpicentRx, Theriva Biologics, Lokon Pharma, DNAtrix, Surv BioPharma Inc., Treovir, Immvira Pharma, Virogin Biotech, OrienGene Biotechnology, Apices Soluciones, Vyriad, Transgene, BioEclipse Therapeutics, Imugene, CG Oncology, Istari Oncology, Akamis Bio, Elicera Therapeutics, and others Key Oncolytic Virus Pipeline Therapies: Pelareorep, Pexa-Vec, CAN-2409, BS001, ParvOryx, Telomelysin, AdAPT-001, VCN-01, LOAd 703, DNX-2401, Surv.m-CRA-1, G207, MVR-T3011, VG161, OrienX010, AloCelyvir, Voyager-V1, TG6002, CRX-100, CF33-hNIS, CG0070, PVS-RIPO, NG-350A, ELC-201, and others Dive deep into rich insights for new oncolytic Virus treatments, visit @ Oncolytic Virus Drugs Table of Contents Related Reports Oncolytic Virus Therapies Market Oncolytic Virus Therapies Market Size, Target Population, Competitive Landscape, and Market Forecast – 2034 report deliver an in-depth understanding of the market trends, market drivers, market barriers, and key oncolytic virus therapies companies including Targovax, Genelux, Imugene, EpicentRx, Replimune, Genelux Corporation, Candel Therapeutics, DNAtrix, SillaJen, Treovir, Lokon Pharma AB, Istari Oncology, CG Oncology, Amgen, Daiichi Sankyo, and others. Melanoma Market Melanoma Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key melanoma companies including IO Biotech, Merck Sharp & Dohme, Eisai, Regeneron Pharmaceuticals, Iovance Biotherapeutics, Highlight Therapeutics, Linnaeus Therapeutics, Spring Bank Pharmaceuticals, Taiga Biotechnologies, Inc., Aivita Biomedical, Inc., Genentech, Inc., Dana-Farber Cancer Institute, BioMed Valley Discoveries, Inc, Amgen, Checkmate Pharmaceuticals, Astellas Pharma Inc, Galectin Therapeutics Inc., Eucure (Beijing) Biopharma Co., Ltd, Mologen AG, Ultimovacs ASA, Seagen Inc., MedImmune LLC, OnKure, Inc., Syntrix Biosystems, Inc., Anaveon AG, iOx Therapeutics, Portage Biotech, ModernaTX, Inc., Nektar Therapeutics, BioNTech SE, Sapience Therapeutics, HUYABIO International, LLC., Provectus Biopharmaceuticals, Inc., Cantargia AB, Turnstone Biologics, Corp., Aura Biosciences, F-star Therapeutics, Inc., Day One Biopharmaceuticals, Inc., Kinnate Biopharma, Xencor, Inc., HiFiBiO Therapeutics, and others. Colorectal Cancer Market Colorectal Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key colorectal cancer companies, including Mirati Therapeutics, Exelixis, Enterome, Arcus Biosciences, Lyell Immunopharma, AstraZeneca, Novartis Pharmaceuticals, Surgimab, Numab Therapeutics, SOTIO Biotech, Amgen, Sichuan Baili Pharmaceutical, Qilu Pharmaceutical, Bristol-Myers Squibb, NGM Biopharmaceuticals, Takeda, PureTech, Pfizer, Kezar Life Sciences, Salubris, Biotherapeutics , and others. Pancreatic Cancer Market Pancreatic Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key pancreatic cancer companies including FibroGen, OSE Immunotherapeutics, Lokon Pharma, Oncotelic Inc., Tesaro, Inc., Helix BioPharma Corporation, Theradex, Tvardi Therapeutics, Incorporated, AIM ImmunoTech Inc., BioNTech SE, Prestige Biopharma Limited, HCW Biologics, Cantex Pharmaceuticals, XBiotech, Inc., Lumicell, Inc., CARsgen Therapeutics Co., Ltd., Panbela Therapeutics, Inc. , and others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP 21% more press release views with Request a Demo

Clinical ResultPhase 2ImmunotherapyFast TrackPhase 3

22 Jul 2025

·endpoints.news

FDA rejects Replimune's oncolytic virus therapy, citing trial design and follow-up study

The FDA on Tuesday issued a complete response letter for Replimune’s oncolytic virus therapy to treat certain patients with advanced melanoma, after taking issue with the company’s design and enrollment of the clinical trial, the company said. The agency said that the study Replimune used in its submission was not “an adequate and well-controlled” trial due to the “heterogeneity” of the patient population, according to a press release from the company. Replimune was attempting to win accelerated approval while enrolling patients in a follow-up study, and the FDA also took issue with the design of that confirmatory study, Replimune said. “We are surprised by this FDA decision and disappointed for advanced melanoma patients who have limited treatment options,” Replimune CEO Sushil Patel said in a statement. “The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews. Additionally, we had also aligned on the design of the confirmatory study.” Replimune’s sharex $REPL cratered early Tuesday morning, falling more than 75%. The company’s comments about the CRL are almost certain to be closely scrutinized by other drug developers as they feel out the agency’s evolving standards under the Trump administration. Replimune was attempting to win approval by testing its therapy RP1 in combination with Bristol Myers Squibb’s PD-1 inhibitor Opdivo. The open-label trial enrolled 140 patients who had previously progressed on an anti-PD-1 drug. There were 75 patients in the study who had received a single-agent PD-1 inhibitor, and 65 who received a combination of anti-PD-1 and anti-CTLA-4 drugs. As of this past June, the trial had been running for over three years, and the median overall survival had not yet been reached. Overall response rate, the study’s primary endpoint, came in at 32.9%, and the three-year survival rate was 54.8%. Comparatively, makers of PD-1 agents have not run many studies in previously treated advanced melanoma, as PD-1 became the new standard of care in the first-line setting about a decade ago. Most trials have tested PD-1 inhibitors after treatment with a CTLA-4. In one such study from 2015, Merck’s Keytruda had an overall response rate of 33.7% when administered every two weeks, though the study was placebo-controlled and the primary endpoint was progression-free survival. RP1 would have become just the second oncolytic virus therapy to receive FDA approval after Amgen’s Imlygic, which came to market in 2015. Imlygic is also approved to treat melanoma, but only in skin and lymph node lesions that can’t be removed by surgery. In an interview ahead of Tuesday’s decision, Patel told Endpoints News that one of the challenges is that there isn’t really a standard of care in advanced melanoma. Many patients are able to have their tumors surgically removed, and if they can’t, they receive PD-1 checkpoint inhibitors, which have been enormously successful. But Patel said that about half of melanoma patients still see their cancers return, usually rapidly upon onset, and often, patients’ only options are chemotherapy or another PD-1 inhibitor. “These tumors become primary or secondary resistant to checkpoint inhibition, and patients really don’t do very well,” Patel said.

Clinical ResultClinical StudyDrug Approval

11 Jul 2025

·www.icr.ac.uk

New combination treatment could overcome immunotherapy resistance in difficult-to-treat cancers

A pioneering clinical trial has demonstrated for the first time that two existing treatments can be combined to potentially improve outcomes for sarcoma and melanoma patients with advanced tumours in their limbs. The researchers delivered a specific cancer-fighting virus to patients undergoing isolated limb perfusion (ILP) – a commonly used technique to deliver chemotherapy to a localised area. In doing so, they were able to activate a whole-body antitumour immune response in addition to a local one. This could prime the body to respond to immunotherapy, opening the door to more effective treatment options. If further clinical trials support these findings, this new treatment combination could transform the lives of patients whose tumour is too advanced to be removed surgically. It could not only help prevent the need for an amputation but also protect the rest of the body from the spread of the cancer. The study was led by researchers at The Institute of Cancer Research, London, and the findings were published in the Journal for ImmunoTherapy of Cancer. The research was funded by the NIHR Biomedical Research Centre at The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust, as well as Sarcoma UK, Amgen Pharmaceuticals, the Robert McAlpine Foundation, the Mabs Mardulyn Charitable Foundation, the Dr Lucy Bull Foundation, and The Royal Marsden Melanoma and Sarcoma Research Fund. Patients with locally advanced melanoma or sarcoma affecting the limbs can face the prospect of amputation due to the extent of the disease. ILP offers the chance to save the affected arm or leg, allowing chemotherapy to be delivered directly to the limb at a high dose that would not be tolerated by the rest of the body. Surgeons achieve this by using a tourniquet and catheters to temporarily isolate the blood circulation of the limb from the rest of the body. Following treatment, they flush the drug from the limb before restoring normal blood circulation. While ILP can shrink or destroy the tumour in question, it typically has no effect on cancerous cells that have spread outside of the limb. This is particularly problematic in sarcoma, as these soft tissue cancers are notoriously difficult to treat. For instance, they, along with some cases of melanoma, are generally resistant to immunotherapy – a form of treatment that helps the body’s immune system recognise and kill cancer cells. The knowledge that immunotherapy has transformed treatment for other cancers drove the researchers to explore combination strategies that could make so-called immunologically “cold” tumours – those surrounded by cells that suppress the immune system – “hotter”, and hence responsive to immunotherapy. The researchers decided to try combining ILP with an oncolytic virus – a type of virus that can target cancer cells, which it preferentially infects and destroys. They opted for talimogene laherparepvec (T-VEC), an oncolytic herpes simplex virus that has been approved as a treatment for melanoma and is known to stimulate immune responses as well as killing tumour cells. In this first-in-human phase I/II trial, 15 patients with either melanoma or sarcoma received injections of T-VEC into their tumours before undergoing ILP. The goals were to enhance the distribution and efficacy of the virus within the tumour and to assess whether this approach could trigger immune responses throughout the body. The findings showed the combination therapy to be well tolerated, with most side effects being mild to moderate. The overall response rate was 53 per cent, and the patients who responded to treatment showed impressive rates of survival, with some remaining disease-free for up to three years following therapy. Importantly, the treatment was able to eliminate cancer for a sustained period in sarcoma subtypes that typically do not respond to ILP alone. To understand how the therapy worked, the team conducted detailed analyses of tumour biopsies and blood samples taken before and after treatment. RNA sequencing revealed that T-VEC increased the expression of genes associated with key immune system activity in tumours, particularly in sarcoma patients. This immune activation was more pronounced in patients who responded to treatment. The team also examined the T-cell receptors present in the samples. This revealed that the patients who responded to the treatment had higher numbers of specific types of T cells in and around their tumours, suggesting an expansion of the subpopulation targeting the cancer. In the blood, these patients had greater TCR diversity, which is indicative of a systemic immune response. This means that although ILP is a localised treatment, the addition of T-VEC appeared to stimulate immune responses that extended beyond the treated limb. These systemic effects are critical, as they suggest the potential for controlling metastatic disease – a major limitation of ILP alone. This study offers compelling evidence that combining oncolytic virotherapy with ILP can transform the complex ecosystem surrounding the tumour and activate robust antitumour immunity, even in cancers traditionally resistant to immunotherapy. Based on the preclinical research they completed before beginning the clinical trial, the researchers believe that it will be possible to increase the response rate further. In the laboratory setting, using an animal model, the researchers were able to direct extremely high doses of oncovirus to the centre of tumours by delivering it as part of the ILP circuit. However, current T-VEC licensing restrictions mean that in the clinical trial, they could only inject the virus into each tumour ahead of the ILP, likely resulting in a lower amount reaching the cancerous cells. Furthermore, while the preclinical work demonstrated that the addition of an immunotherapy agent to the combination treatment completely prevented the development of secondary cancers, the researchers did not include one in this clinical trial – the first trial of this approach. Reflecting on the significance of the trial, first author Professor Andrew Hayes, Consultant General Surgeon and Surgical Oncologist at the Sarcoma Unit and the Skin Unit at The Royal Marsden and an Honorary Faculty at the ICR, said: “While this trial was small, the results are promising and lay the groundwork for larger studies. We have shown that we can harness the power of oncolytic viruses to not only improve local control of limb tumours but also stimulate systemic immunity. For sarcoma patients, who have historically had few immunotherapy options, this could be a game-changer. “Patients with large, advanced sarcomas carry an extremely high risk of secondary spread, and amputation sadly does not take away that risk. The potential of a combination treatment that both avoids the need for an amputation and diminishes the risk of spread is, therefore, very important.” Senior author Professor Alan Melcher, Group Leader of the Translational Immunotherapy Group at the Institute of Cancer Research, said: “We’re seeing that oncolytic virotherapy, when delivered via isolated limb perfusion, can turn immunologically cold tumours into hot ones. This opens up exciting possibilities for combining regional and systemic treatments to tackle cancers that were previously untouchable by immunotherapy. “Our future research is likely to focus on optimising dosing, timing and combinations with various immunotherapies to maximise efficacy. We very much hope that the potential benefits of this treatment strategy will offer new optimism to patients facing difficult diagnoses.” Image credit: Phylum from Pixabay

ImmunotherapyClinical ResultClinical Study

100 Deals associated with Talimogene laherparepvec

External Link

KEGG	Wiki	ATC	Drug Bank
D09966	Talimogene laherparepvec	L01XX51	DB13896

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Unresectable Melanoma	European Union	Amgen Europe BV	16 Dec 2015
Unresectable Melanoma	Iceland	Amgen Europe BV	16 Dec 2015
Unresectable Melanoma	Liechtenstein	Amgen Europe BV	16 Dec 2015
Unresectable Melanoma	Norway	Amgen Europe BV	16 Dec 2015
Melanoma	United States	Amgen, Inc.	27 Oct 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Squamous cell carcinoma of head and neck metastatic	Phase 3	United Kingdom	Amgen, Inc.	16 Dec 2015
Locally Advanced Head and Neck Squamous Cell Carcinoma	Phase 3	United States	Amgen, Inc.	01 Feb 2011
Locally Advanced Head and Neck Squamous Cell Carcinoma	Phase 3	United Kingdom	Amgen, Inc.	01 Feb 2011
Locally Advanced Soft Tissue Sarcoma	Phase 2	United States	Amgen, Inc.	03 Mar 2025
Locally Advanced Melanoma	Phase 2	United States	Amgen, Inc.	21 May 2020
Metastatic melanoma	Phase 2	Greece	Amgen, Inc.	03 Dec 2019
Brain metastases	Phase 2	United States	CareFusion Corp.	06 Mar 2019
Brain metastases	Phase 2	United States	Amgen, Inc.	06 Mar 2019
Lung Cancer	Phase 2	United States	Amgen, Inc.	06 Mar 2019
Lung Cancer	Phase 2	United States	CareFusion Corp.	06 Mar 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03802604 (SOLTI-1503 PROMETEO, Pubmed \| Nat Commun)	Phase 2	HER2-negative breast cancer Neoadjuvant HER2-negative	28	Talimogene laherparepvec + Atezolizumab	ihjujcubfk(eohjyiyacm) = dyzyzpffpv olkrezqjpd (rpuevlznho )	Positive	16 Feb 2026
NCT03069378 (CTgov)	Phase 2	Hemangiosarcoma	41	Pembrolizumab+T-Vec	ldbgvrixgi = lcbpjpzlku azldeybthb (ossdbzbejf, nktoxrdzhn - qgehekxqyy) View more	-	29 Oct 2025
ESMO2025	Not Applicable	Unresectable Melanoma	458	anti-PD1	icqbnikqep(gbmjqbicul) = dwnwnxvpxh avidzhfozk (xreuuwqrib, 32.4 - 64.7) View more	Positive	17 Oct 2025
ESMO2025	Not Applicable	Unresectable Melanoma	458	T-VEC	icqbnikqep(gbmjqbicul) = bqxzhualgr avidzhfozk (xreuuwqrib ) View more	Positive	17 Oct 2025
NCT02779855 (phase 1/2 trial, ASCO2025)	Phase 1/2	Triple Negative Breast Cancer Neoadjuvant	-	Talimogene laherparepvec (TVEC) + neoadjuvant chemotherapy (NACT)	titdsrlfft(nwhodrrwso) = hswutvpstw zntgtjonaa (bcmzqcklfy, 30.9 - 60.9) View more	Positive	30 May 2025
NCT03886311 (ASCO2025)	Phase 2	Leiomyosarcoma	35	Talimogene Laherparepvec + Nivolumab + Trabectedin	cterysitzp(wfzmoityon) = lwfvntckku uwofovgpsz (cdfvldflhu ) View more	Positive	30 May 2025
NCT03886311 (ASCO2025)	Phase 2	Leiomyosarcoma	35	Trabectedin	ioosnmfatv(fvfvplvkcy) = ulxyzocsdn cdqvfgzqtw (toozbhdhme )	Positive	30 May 2025
NCT03802604 (SOLTI-PROMETEO, ESMO_BC2025)	Phase 2	Early Stage Breast Carcinoma Neoadjuvant HER2-negative	28	Talimogene laherparepvec (T-VEC) + Atezolizumab	gmfayezosm(ogrltwqqxw) = lekukaezoy ffgeqogbri (snvckcqszf )	Positive	15 May 2025
Phase 2 Study (ASGCT2025)	Phase 2	Leiomyosarcoma \| Liposarcoma	35	Talimogene Laherparepvec, Nivolumab, Trabectedin	ulhmrdindh(kkopfwyxux) = xzmvmaliyt mvhhqvaitl (jwuecfjwfw ) View more	Positive	13 May 2025
Phase 2 Study (ASGCT2025)	Phase 2	Leiomyosarcoma \| Liposarcoma	35	Trabectedin	kqfrbfrhza(duegnwgywi) = kscwcxmmxt lfljrekyph (yjucquijcq )	Positive	13 May 2025
NCT02509507 (Pubmed \| Oncologist)	Phase 1/2	Hepatocellular Carcinoma \| Advanced Malignant Solid Neoplasm	-	Talimogene laherparepvec (T-VEC) + Pembrolizumab	tuyogoxhcg(larazjsdsi) = mifymiczkr jyklpkjrsh (xicfixdxqt, 1.0 - 27.0)	Negative	10 Mar 2025
NCT02819843 (CTgov)	Phase 2	Melanoma, Cutaneous Malignant \| Merkel Cell Carcinoma	19	TALIMOGENE LAHERPAREPVEC (Intralesional TALIMOGENE LAHERPAREPVEC Without Radiotherapy)	xhjkbbhggl = pdpldnjwvd pgroankbvt (afgtzbkwoi, wvmwbxwbtb - sznhzmwhvw) View more	-	29 Jan 2025
NCT02819843 (CTgov)	Phase 2	Melanoma, Cutaneous Malignant \| Merkel Cell Carcinoma	19	Hypofractionated Radiotherapy+TALIMOGENE LAHERPAREPVEC (Intralesional TALIMOGENE LAHERPAREPVEC With Radiotherapy)	xhjkbbhggl = pgkcvkwkxf pgroankbvt (afgtzbkwoi, lsfduyzbde - vhkuclxeqh) View more	-	29 Jan 2025
NCT03086642 (Pubmed \| Oncologist) Manual	Phase 1	Pancreatic Cancer	9	Talimogene laherparepvec	xavglgfsuc(jxlqyvabep) = ipojyddvqk teoqwoqizi (vfwbwbuydx ) View more	Positive	02 Dec 2024

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