Cavatak (gebasaxturev) / Merck (MSD) - LARVOL DELTA

LUNGS TO HEART: A CASE REPORT ON COXSACKIE B-INDUCED PERICARDITIS PRESENTING WITH RESPIRATORY DISTRESS (CHEST 2025) - "The patient was started on treatment for acute pericarditis with an Ibuprofen for symptomatic relief...Coxsackievirus A21 and EV68 are the predominant serotypes that cause acute respiratory tract infection in adults... This case highlights the importance of early identification of at-risk patients with poor immune status and physical health, which can lead to permanent heart damage or death."

Case report • Clinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Cough • Dementia • Diabetes • Epilepsy • Fatigue • Hypertension • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Otorhinolaryngology • Pneumonia • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

KEYMAKER-U02 Substudy 02C: Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=146 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | N=90 ➔ 146

Enrollment change • Trial completion • Melanoma • Oncology • Solid Tumor

KEYMAKER-U02 Substudy 02C: Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=90 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2030 ➔ Oct 2025 | Trial primary completion date: Apr 2030 ➔ Oct 2025

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Effect of CVA21, an Oncolytic Virus, in combination with Pembrolizumab on immunogenicity and the tumour microenvironment in advanced NSCLC: a phase I/II trial. (PubMed, Clin Cancer Res) - "This study demonstrates the potential of CVA21 to modulate the immunogenicity of tumor cells and remodelling the tumor microenvironment, providing novel insights for patient selection for trials involving novel immunotherapeutic approaches."

IO biomarker • Journal • P1/2 data • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • PD-L1 • TMB

Role of Antidrug Antibodies in Oncolytic Viral Therapy: A Dynamic Modelling Approach in Cancer Patients Treated with V937 Alone or in Combination. (PubMed, Clin Pharmacokinet) - "This quantitative and (semi-) mechanistic framework can be expanded to other oncolytic viruses and used to explore under which scenarios a relevant impact could be observed, thus supporting the development of novel oncolytic viral therapies."

Journal • Oncology

Proffered Paper: Oncolytic virus (CVA21) in combination with pembrolizumab increases tumour cell immunogenicity and remodels the tumour microenvironment in advanced NSCLC: a phase I/II trial (EACR 2025) - "The combination of CVA21 and pembrolizumab is safe and shows promising efficacy in ICI pre-treated patients with advanced NSCLC. Our translational multi-omic analysis provides insights that may enhance patient selection for future trials investigating novel immunotherapeutic strategies."

Combination therapy • IO biomarker • Metastases • Oncolytic virus • P1/2 data • Tumor cell • Tumor microenvironment • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • PD-L1 • TMB

Enterovirus C recombination groups: RNA sequence similarity and the viral polymerase underpin sexual replication mechanisms. (PubMed, J Virol) - "To test this hypothesis, we focused on recombination between two related group C enteroviruses, poliovirus and Coxsackievirus A21 (CVA21), using bioinformatic, biological, and biochemical approaches...In this study, we clarify which viruses recombine with one another in nature and further elucidate the mechanisms by which the viral polymerase distinguishes between related and unrelated RNA templates-a sexual form of replication. Understanding these mechanisms could lead to better strategies for virus control and/or eradication."

Journal

Minimizing batch-to-batch variability of a live virus vaccine by process analytical technologies. (PubMed, Biotechnol Prog) - "For bioprocesses producing live virus, such as enterovirus Coxsackievirus A21, viral titer (infectivity basis) decay rates can exceed 30% within a day...Even when a process deviation in inoculated cell density occurred, causing a significant shift in viral titer kinetics, the PAT harvest triggers yielded greater than 87% of peak titer. By comparison, the time-based harvest yielded 16%."

Journal

Arming an RNA-Based Oncolytic Picornavirus Platform Using LNPs for Replicon Co-Delivery (ASGCT 2025) - "Previous studies, including our own, have demonstrated the feasibility of formulating oncolytic picornaviruses as infectious RNA (iRNA) using Coxsackievirus A21 (CVA21), a clinically developed oncolytic virus...This work supports the continued development of mengovirus as an RNA-based oncolytic virus platform and the use of replicons as RNA-based arming factors. Disease Focus of Abstract:Cancer Hematologic"

IO biomarker • Oncolytic virus • Hematological Malignancies • Oncology

Preparation and antitumor activity characterization of oncolytic nanoparticles encapsulating CVA21 (PubMed, Sheng Wu Gong Cheng Xue Bao) - "These findings suggest that CVA21@ONP can replicate and survive extensively both in vitro and in vivo, activating the immune system of mice administrated with CVA21@ONP to target cells at the tumor site, thereby remodeling the tumor immune microenvironment and accelerating the suppression or even complete regression of tumors. The oncolytic performance of CVA21@ONP has been verified through intratumoral injection administration in this study, aimed at further exploring its therapeutic potential and promoting the development of the field of tumor treatment."

Journal • Oncology

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial. (PubMed, Nat Med) - P1/2 | "Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Longer follow-up will provide insight into the incremental benefit of combining neoadjuvant pembrolizumab with other therapies in stage IIIB-D melanoma. ClinicalTrials.gov registration: NCT04303169 ."

IO biomarker • Journal • P1/2 data • Tumor mutational burden • Melanoma • Oncology • Solid Tumor • TIGIT • TMB

Combination of oncolytic viruses, radiation therapy, and immune checkpoint inhibitor treatment in a breast cancer model (ESMO-IO 2024) - "We demonstrated that a combination of Echovirus 7, Enterovirus B75, Coxsackievirus A21, and Poliovirus Type 3 with radiation therapy and immune checkpoint inhibitors (ICIs) shows efficacy in in vivo breast cancer models.Methods Breast cancer cell line 4T1-PVR (expressing human poliovirus receptor PVR/CD155), were obtained through lentiviral transduction...Treatment with the PD-L1 inhibitor alone had no effect on tumor growth, indicating that the tumor was resistant to ICI. Therapeutic responses were associated with increased infiltration of CD45+ immune cells into the tumor, including an increase in CD8+ T cells and a decrease in regulatory T cells.Conclusions In a preclinical surrogate model, the triple combination of oncolytic viruses, radiation, and immune checkpoint inhibition resulted in increased tumor infiltration by CD8+ T cells, correlating with reduced tumor volumes and improved animal survival."

Checkpoint inhibition • Oncolytic virus • Preclinical • Breast Cancer • Oncology • Solid Tumor • CD8 • ITGAM • PTPRC • PVR

Oncolytic Coxsackievirus B3 Strain PD-H Is Effective Against a Broad Spectrum of Pancreatic Cancer Cell Lines and Induces a Growth Delay in Pancreatic KPC Cell Tumors In Vivo. (PubMed, Int J Mol Sci) - "In vitro, PD-H exhibited robust replication, as measured by plaque assays, and potent lytic activity, as assessed by XTT assays, in most pancreatic tumor cell lines, outperforming two other coxsackievirus strains tested, H3N-375/1TS and CVA21...Although pancreatic tumors respond to PD-H treatment, its therapeutic efficacy is limited. Combining PD-H with other treatments, such as those aiming at reducing the desmoplastic stroma which impedes viral infection and spread within the tumor, may enhance its efficacy."

IO biomarker • Journal • Oncolytic virus • Preclinical • Gastrointestinal Cancer • Hepatology • Infectious Disease • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • CASP7

Clinical and Genomic Epidemiology of Coxsackievirus A21 and Enterovirus D68 in Homeless Shelters, King County, Washington, USA, 2019-2021. (PubMed, Emerg Infect Dis) - "Phylogenetically clustered CVA21 and EV-D68 cases occurred in some shelters. Some shelters also hosted multiple CVA21 lineages."

Journal • Review • Infectious Disease • Respiratory Diseases

KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) and investigational agents followed by adjuvant pembro for stage IIIB-D melanoma (ESMO 2024) - P1/2 | "We present initial results from arm 4 (pembro + MK-4830 [anti-ILT4]) and arm 5 (favezelimab [anti-LAG-3] coformulated with pembro [fave/pembro]) and updated results from arm 1 (pembro + vibostolimab [vibo; anti-TIGIT]), arm 2 (pembro + gebasaxturev [geba; coxsackievirus A21]), and arm 3 (pembro alone). Adults with resectable stage IIIB-D melanoma were randomly assigned to open arms. All arms had manageable safety in stage IIIB-D melanoma. With the promising antitumor activity observed in this study, further investigation of pembro + vibo and fave/pembro in this setting is warranted. RFS by major pathologic response will be presented."

Clinical • Melanoma • Oncology • Solid Tumor • TIGIT

Treatment of malignant melanoma with coxsackievirus A21 (V937): An emerging oncolytic virotherapy. (PubMed, Exp Dermatol) - "In addition to reporting manageable safety profiles, clinical trial data examining intratumoral V937 combination therapy with pembrolizumab and ipilimumab also endorsed favourable objective response rates compared to immune checkpoint inhibitor monotherapy (47% vs. 38% and 21% vs. 10%, respectively). Although small subsets of patients experienced severe adverse effects and study design limitations imposed constraints on collected data, evidence for the efficacy of V937 remains encouraging. With few clinical trials evaluating V937 in melanoma, additional data is required before routine usage in standard treatment for metastatic lesions."

Journal • Oncolytic virus • Review • Melanoma • Oncology • Solid Tumor

Disentangling Anti-Tumor Response of Immunotherapy Combinations: A Physiologically Based Framework for V937 Oncolytic Virus and Pembrolizumab. (PubMed, Clin Pharmacol Ther) - "Additionally, this platform allows us to investigate not only the contribution of processes related to the viral kinetics and dynamics on tumor response, but also the influence of its interaction with an ICI. Additionally, the model can be used to explore different scenarios aiming to optimize treatment combinations and support clinical development."

Journal • Oncolytic virus • Oncology • CD8 • PD-1 • PD-L1

Oncolytic virus V937 in combination with PD-1 blockade therapy to target immunologically quiescent liver and colorectal cancer. (PubMed, Mol Ther Oncol) - "In addition, both recombinant interferon-gamma and pembrolizumab increased ICAM-1 on tumor cell lines or organoids and, in turn, amplified V937-mediated oncolysis and immunogenicity. These findings provide critical mechanistic insights on the cross-talk between V937-mediated oncolysis and immune responses, demonstrating the therapeutic potential of V937 in combination with PD-1 blockade to treat immunologically quiescent cancers."

Combination therapy • Journal • Oncolytic virus • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor • ICAM1 • IFNG • TERC

Development of a robust cell-based potency assay for a coxsackievirus A21 oncolytic virotherapy. (PubMed, Heliyon) - "Furthermore, the plaque assay quantifies OV infectivity with better precision (32% vs 58%), with higher sample throughput (22 samples/week vs 3 samples/week) and shorter assay turnaround time (4 days vs 7 days) than the TCID50 method. This assay development strategy can provide guidance for the development of robust cell-based potency methods for OVs and other infectious viral products."

Journal • Oncolytic virus • Infectious Disease • Oncology

A Study of Gebasaxturev (V937) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (V937-013) (clinicaltrials.gov) - P1/2 | N=75 | Terminated | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P1b/2 ➔ P1/2 | Completed ➔ Terminated; Business Reasons

Combination therapy • Metastases • Phase classification • Trial termination • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • ER • HER-2 • PD-L1 • PGR

The Preclinical Profile of Maturation Inhibitor VH3739937 (CROI 2024) - "Background: VH3739937 (VH937) is a next generation maturation inhibitor (MI) currently in clinical trials. The pre-clinical virology profile of VH937 supported the progression of this MI into clinical development."

Preclinical • Human Immunodeficiency Virus • Infectious Disease

Efficacy, Safety, and Tolerability of Gebasaxturev (V937) Administered Intravenously or Intratumorally With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone in Participants With Advanced/Metastatic Melanoma (V937-011) (clinicaltrials.gov) - P2 | N=85 | Terminated | Sponsor: Merck Sharp & Dohme LLC | Completed ➔ Terminated; Business Reasons

Combination therapy • Metastases • Trial termination • Melanoma • Oncology • Solid Tumor • CD4

The Effects of Mesenchymal Stem Cells Loaded with Oncolytic Coxsackievirus A21 on Mouse Models of Colorectal Cancer. (PubMed, Curr Cancer Drug Targets) - "The results of the current study suggest that MSCs loaded with oncolytic CVA21 therapy for the CRC mouse model may have some potential advantages. On the other hand, the results of the study showed that, in addition to activating the acquired immune system, the use of MSCs loaded with oncolytic CVA21 also stimulates the innate immune system by increasing levels of nitric oxide."

Journal • Oncolytic virus • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IFNG • IL10 • IL4 • TGFB1

KEYMAKER-U02 Substudy 02C: Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=90 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Melanoma • Oncology • Solid Tumor

The efficacy and safety assessment of oncolytic virotherapies in the treatment of advanced melanoma: a systematic review and meta-analysis. (PubMed, Virol J) - "Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma."

Journal • Metastases • Oncolytic virus • Retrospective data • Review • Dermatology • Herpes Simplex • Melanoma • Oncology • Pain • Pruritus • Solid Tumor • CSF2