Imlygic (talimogene laherparepvec) / Amgen - LARVOL DELTA

Multi-omics analysis of longitudinal melanoma samples reveals evolutionary transitions and therapy-associated cell-state switching (AACR 2026) - "Combination of anti-PD1 and intralesional T-VEC therapy reshaped the genomic landscape of tumor clones, selectively favoring L3, which expanded into clonality while L1 became undetectable, consistent with therapy-associated selection... This study reconstructed a phylogenetic map for tumor evolution through multi-omics, longitudinal data from an ITM patient to reveal key pathways and tumor state changes associated with metastatic events and heterogeneity in clinical responses. In the next step, the individual phylogenetic trees will be compared with other patients in the cohort to explore intra-tumoral, inter-tumoral, and inter-patient heterogeneity in tumor progression, metastasis sites, and resistance to therapy."

IO biomarker • Melanoma • Oncology • Solid Tumor • AXL • MITF

Modulating the tumor microenvironmentwith an engineered oncolytic herpesvirus facilitates potent antitumor response (AACR 2026) - "However, this synergy is yet to be demonstrated: in a randomized, double blind, phase III trial, the HSV based talimogene laherparepvec (TVEC) in combination with anti-PD1 ICI therapy failed to improve both progression free survival and overall survival relative to anti-PD1 therapy alone...Together, these effects should cooperate with STING activation from DN146 to broadly reprogram the tumor microenvironment. When tested in a bilateral, murine colorectal cancer model, this virus achieves clearance of both locally injected and distal un-injected tumors, indicating strong local and systemic antitumor effects."

Biomarker • Oncolytic virus • Tumor microenvironment • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • SIRPA • STING

Hydrogel Micro/Nanostructures for the Delivery of Oncolytic Viruses: Overcoming Limitations and Improving Efficacy. (PubMed, Adv Pharm Bull) - "Despite milestone achievements in the development of OVs, which led to the U.S. Food and Drug Administration (FDA) approval of talimogene laherparepvec (T-VEC) in 2015 against melanoma, there are some hurdles limiting their translation from the bench to the clinic, such as non-specific localization, host immune response against OVs and their clearance, and low efficiency as a monotherapy...Hydrogels, with their tunable characteristics and versatile properties, offer a promising platform for the controlled release, precise delivery, and therapeutic enhancement of OVs in combination with other therapeutic agents in the treatment of cancers. This review aims to provide a deep insight into the types and development of OVs and their application in clinical trials and then will discuss the characteristics of hydrogels and how they improve the therapeutic efficacy of OVs."

Journal • Review • Melanoma • Oncology • Solid Tumor

Oncolytic Viruses in Cancer Immunotherapy: From Molecular Engineering to Clinical Translation. (PubMed, Cells) - "These innovations have propelled significant clinical progress, exemplified by the approvals of talimogene laherparepvec (T-VEC), G47Δ, and H101, and have driven a surge of combination trials integrating OVs with immune checkpoint blockade, adoptive cell therapies, radiotherapy, and targeted therapies to overcome multilayered tumor immune resistance...By integrating advanced viral engineering with rational combination strategies and innovative delivery technologies, OVs hold substantial potential to overcome current barriers in cancer immunotherapy and advance precision oncology. Continued translational research will be essential to fully harness their therapeutic impact and broaden their clinical applicability."

Journal • Review • Immune Modulation • Immunology • Infectious Disease • Oncology

ASO Visual Abstract: Evaluation of Talimogene Laherparepvec for the Treatment of Advanced Nonmelanoma Skin Cancers. (PubMed, Ann Surg Oncol) - "Our work highlights the fact that durable response to T-VEC for patients with advanced NMSC is possible in the setting of a high rate of concurrent immune therapy administration. Further work should more rigorously explore the role that T-VEC may play in NMSC, with particular attention to its use with immune therapy ( https://doi.org/10.1245/s10434-026-19182-3 )."

Journal • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma

Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=50 | Completed | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Feb 2026 ➔ Aug 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Enhanced Antitumor Activity and Induction of Immunogenic Cell Death in NUT Carcinoma Cells by Combining Oncolytic Viruses with the Dual Inhibitor NEO2734. (PubMed, Viruses) - "To investigate multimodal therapeutic approaches that combine epigenetic modulation with immunogenic and cytotoxic effects of oncolytic viruses (OVs), we evaluated two recombinant OVs, including the herpes simplex virus talimogene laherparepvec (T-VEC) and a measles vaccine virus (MeV-GFP), in combination with NEO2734 in four distinct NC cell lines. Evaluation of immunogenic cell death (ICD) markers displayed elevated ATP and HMGB1 levels and increased surface calreticulin with T-VEC and NEO2734 combinations. Overall, these findings indicate that combining OVs with BET/p300 inhibitors elicits potent antitumor responses, supports synergistic interactions and immunogenicity, and warrants further investigation in multimodal therapeutic strategies for NC."

IO biomarker • Journal • Herpes Simplex • Infectious Disease • Measles • NUT Midline Carcinoma • Oncology • BRD4 • CALR • HMGB1 • NUTM1

Evaluation of Talimogene Laherparepvec for the Treatment of Advanced Nonmelanoma Skin Cancers. (PubMed, Ann Surg Oncol) - "Our initial experience with a small, single-institution cohort demonstrated tumor response to intralesional T-VEC with or without immunotherapy in some patients with NMSC. Nearly 50% of participants had a complete response; two-thirds of responders remained relapse-free at the time of follow-up. Some observed responses are not attributable to T-VEC alone due to high usage rates of IO. Future work should expand to larger cohorts and focus on its use with and without immune therapy."

Journal • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma

A Decade of Oncolytic Virotherapy in Pediatric Cancers: A Systematic Review of Safety, Immune Awakening, and Emerging Efficacy. (PubMed, Cureus) - "Investigated viral platforms included herpes simplex virus type 1 (G207, HSV1716), adenovirus (DNX-2401, ICOVIR-5, Ad-TD-nsIL12), T-VEC (HSV-1), poliovirus (PVSRIPO), Seneca Valley virus, and reovirus. Overall risk of bias was moderate, while the certainty of evidence was rated as low for safety outcomes and very low for efficacy. These findings indicate that oncolytic virotherapy is safe, feasible, and biologically active in children with malignant brain and solid tumors, and that preliminary survival signals and consistent immune activation support further investigation through larger, multicenter randomized trials and combination strategies with radiotherapy or immune checkpoint inhibitors."

Journal • Review • Brain Cancer • CNS Tumor • Glioma • Herpes Simplex • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • CD8 • IFNG • IL6

Talimogene laherparepvec and atezolizumab in HER2-negative breast cancer following neoadjuvant chemotherapy: a window-of-opportunity phase II trial (SOLTI-1503 PROMETEO). (PubMed, Nat Commun) - P1 | "The trial met its pre-specified efficacy and safety endpoints. These findings support the feasibility of T-VEC plus atezolizumab as a  preoperative immunotherapy approach for managing HER2-negative residual disease post-neoadjuvant chemotherapy and warrant further exploration in larger trials."

IO biomarker • Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Combination of talimogene laherparepvec (T-VEC) with atezolizumab (atezo) in patients (pts) with residual breast cancer (BC) after standard neoadjuvant chemotherapy (NAC): Survival results of the SOLTI-PROMETEO study (ESMO-BC 2025) - P1 | "Adjuvant treatments included chemotherapy (n=6), endocrine therapy (n=19), and abemaciclib (n=1). Despite the limited sample size, this analysis of PROMETEO suggests that achieving a pCR with T-VEC and atezo in pts with RD after standard multi-agent CT is associated with improved survival outcomes. These results underscore the potential of trials with this design to identify effective drugs for escalating treatment in poor-prognosis populations of pts with HER2- BC."

Clinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Strategically engineering an oncolytic herpes simplex virus to improve systemic delivery. (PubMed, Mol Ther Oncol) - "Despite the recent regulatory approvals of oncolytic viruses such as T-VEC (JS1/34.5-/47-/GM-CSF), Oncorine (H101), and Teserpaturev (G47Δ), the clinical impact of OV remains limited by its reliance on intratumoral administration. Preclinical studies demonstrate that FusOn-SD efficiently reaches tumor sites following systemic administration, exhibiting enhanced immune evasion and oncolytic potency. These findings position FusOn-SD as a promising candidate for advancing OV beyond localized injections, with the potential to transform virotherapy into a viable treatment for metastatic cancer."

Journal • Herpes Simplex • Oncology • CSF2

Interim analysis of a phase II study of talimogene laherparepvec (T-VEC) followed by combination T-VEC + nivolumab in non-melanoma skin cancers and refractory cutaneous lymphoma (NCI#10057) (SITC 2024) - "Conclusions Analysis of data from Part I of this clinical trial suggests that T-VEC monotherapy did not translate to broad clinical efficacy across all tumor types, though may show activity in patients without visceral metastases. MCC and CSCC expansion cohorts (Part II) will be reported separately.View this table:View inline View popup Download powerpoint Abstract 621 Table 1 Best response to T-VEC monotherapyDownload figure Open in new tab Download powerpoint Abstract 621 Figure 1 Elderly female with at least 4 in-transit metastases from MCC on the left lower leg, who achieved a durable PR on T-VEC monotherapy"

IO biomarker • P2 data • Hematological Malignancies • Lymphoma • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CCL23 • CTAG1B • TRB

Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial. (PubMed, J Immunother Cancer) - P1b/2 | "No new safety signals were reported.At the 5-year follow-up, the improved response rates observed with T-VEC plus ipilimumab were durable. This is the first randomized controlled study of the combination of an oncolytic virus and a checkpoint inhibitor that meets its primary end point.Trial registration number: NCT01740297."

Combination therapy • Journal • Metastases • P2 data • Melanoma • Oncology • Solid Tumor

Postmarketing Prospective Study of Melanoma Patients Treated With IMLYGIC® to Characterize Risk of Herpetic Infection (clinicaltrials.gov) - P=N/A | N=187 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Melanoma • Oncology • Solid Tumor

TVEC and Preop Radiation for Sarcoma (8 ml Dose) (clinicaltrials.gov) - P1/2 | N=8 | Active, not recruiting | Sponsor: John Rieth | Trial completion date: Nov 2027 ➔ Feb 2028

Trial completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Talimogene Laherparepvec and Panitumumab for the Treatment of Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: Rutgers, The State University of New Jersey | Active, not recruiting ➔ Terminated; slow accrual

Trial termination • Tumor mutational burden • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Feasibility and Tolerability of IMLYGIC for the Treatment of Cutaneous Neurofibromas in Adults With NF1 (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Johns Hopkins University | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

Primary results of SOLTI-1503 PROMETEO phase 2 trial of Combination of Talimogene Laherparepvec (T-VEC) with Atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy (SABCS 2022) - P1 | "Two months of T-VEC in combination with atezolizumab induced a pCR in a subgroup of pts with chemoresistant HER2- breast cancer. This effect is probably related to the immune activation provoked by the combined treatment. Interestingly, a high discrepancy was observed between the pre-surgical radiological imaging and the actual surgical pathological report."

Clinical • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1 • TMB

Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2026 ➔ Dec 2026 | Trial primary completion date: May 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma

Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. (PubMed, J Clin Oncol) - "T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone."

Clinical • Journal • P3 data • Melanoma • Oncology • Solid Tumor

Safety and feasibility of talimogene laherparepvec in peritoneal surface malignancies: Results from the TEMPO trial. (PubMed, Mol Ther Oncol) - P1 | "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."

Journal • Hematological Disorders • Herpes Simplex • Neutropenia • Oncology • Peritoneal Cancer

Overcoming resistance in oncolytic virotherapy: Nano-engineered solutions for systemic delivery and efficacy boost. (PubMed, Drug Resist Updat) - "Despite clinical advancements, including the FDA-approved T-VEC and subsequent agents, significant challenges remain, particularly in systemic delivery and therapeutic efficacy optimization...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."

Journal • Review • Oncology

Oncolytic Viruses in Glioblastoma: Clinical Progress, Mechanistic Insights, and Future Therapeutic Directions. (PubMed, Cancers (Basel)) - "Key observations include the encouraging clinical trajectory of oHSV exemplars-T-VEC (approved for melanoma) and G47Δ (approved in Japan for recurrent GBM)-the multi-center exploration of the adenovirus DNX-2401 combined with programmed death-1 (PD-1) blockade, and the early-stage status of reovirus (pelareorep) and Newcastle disease virus programs. Future directions encompass programmable vector design, optimization of systemic delivery, biomarker-guided patient selection, and rational combination immunotherapy. Collectively, OVs represent a promising immunotherapeutic strategy in GBM; further gains will hinge on vector engineering and precision combinations to translate mechanistic promise into durable clinical benefit."

IO biomarker • Journal • Review • Brain Cancer • Glioblastoma • Glioma • Herpes Simplex • High Grade Glioma • Melanoma • Oncology • Solid Tumor

Melanosis Secondary to Drugs: A Real-World Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS). (PubMed, Skin Res Technol) - "Patients who experience drug-induced melanosis generally have bad outcomes, underscoring the imperative for heightened clinical surveillance regarding the risk of drug-induced melanosis."

Adverse events • Journal • Real-world evidence • Retrospective data