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

KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma (AACR 2023) - P1/2 | "Neoadjuvant pembro + vibo, pembro + geba, and pembro alone followed by adjuvant pembro had manageable safety and promising antitumor activity in patients with stage IIIB-D melanoma. Of the combination treatments, pembro + vibo showed the most promise."

Clinical • Melanoma • Oncology • Solid Tumor • TIGIT

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

Intratumoral oncolytic virus V937 plus ipilimumab in patients with advanced melanoma: the phase 1b MITCI study. (PubMed, J Immunother Cancer) - P1b | "Responses associated with intratumoral V937 plus ipilimumab were robust, including in the subgroup of patients who had experienced disease progression on prior anti-PD-1 therapy. Toxicities were manageable and consistent with those of the individual monotherapies."

Journal • Metastases • Oncolytic virus • P1 data • Dermatology • Fatigue • Hepatology • Melanoma • Oncology • Pruritus • Solid Tumor

Updated oncolytic viruses for the treatment of bladder cancer: a systematic review. (PubMed, Iran J Microbiol) - "Various oncolytic viruses were investigated, either as monotherapies or in combination with other agents, including Vaccinia virus, Adenovirus, Oncolytic adenovirus ONYX, Coxsackievirus A21 (CVA21), oncolytic CVA21 (V937), attenuated measles virus (MV-NIS virus), recombinant adenovirus (rAd), and a serotype 5 adenovirus engineered to express GM-CSF...The common virus was the non-replicative recombinant adenovirus serotype 5 (Ad5), which encodes human interferon alfa-2b (IFNα2b) a cytokine with anti-tumor properties. It is administered via intravesical instillation and has received FDA approval."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Measles • Oncology • Solid Tumor • Urology • CSF2 • IFNA1

Concordance of pathologic response assessment between local and central review in melanoma: a post hoc analysis of KEYMAKER-U02 substudy 02C. (PubMed, ESMO Open) - "These results confirm a high level of concordance in pathologic response assessment between local and central review and among central reviewers and provide confidence in the accuracy of pathologic response assessment following neoadjuvant therapy."

Journal • Retrospective data • Melanoma • Oncology • Solid Tumor

Re-evaluating melanoma treatment: a comparative look at herpes simplex virus and coxsackievirus oncolytic therapies in advanced melanoma: a meta-analysis of clinical trials. (PubMed, Melanoma Res) - "Among ICIs pembrolizumab showed the most favorable outcomes...HSV monotherapy or CSV may be favored when minimizing toxicity is a priority, even if it comes at the cost of some reduced response rate. However, combining CSV with ICIs may surpass talimogene laherparepvec monotherapy in efficacy because of the reduced likelihood of tumor resistance."

Journal • Retrospective data • Genetic Disorders • Herpes Simplex • Melanoma • Oncology • Skin Cancer • Solid Tumor

Oncolytic Virotherapy and Immunogenic Cell Death: Mechanisms, Platforms, and Clinical Translation. (PubMed, Viruses) - "Coxsackievirus A21 combined with pembrolizumab achieved a 47% objective response rate in melanoma in the CAPRA trial, representing notable efficacy exceeding either monotherapy. Japanese researchers have pioneered microRNA-targeted Coxsackievirus B3, achieving cardiac safety attenuation while preserving complete oncolytic potency and ICD-inducing capacity. This comprehensive analysis synthesizes molecular mechanisms, platform comparisons, clinical efficacy data, and translational challenges to guide future development of oncolytic virotherapy as a cornerstone of cancer immunotherapy."

Journal • Review • Melanoma • Oncology • Solid Tumor • Thoracic Cancer • CALR • CTLA4 • HMGB1 • ICAM1 • PD-1 • PD-L1

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

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