- |||||||||| Cavatak (gebasaxturev) / Merck (MSD)
Review, Journal, Oncolytic virus: Treatment of malignant melanoma with coxsackievirus A21 (V937): An emerging oncolytic virotherapy. (Pubmed Central) - Sep 1, 2024
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.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Journal, Oncolytic virus: Disentangling Anti-Tumor Response of Immunotherapy Combinations: A (Pubmed Central) - Jul 22, 2024
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.
- |||||||||| Cavatak (gebasaxturev) / Merck (MSD)
Journal, Combination therapy, Oncolytic virus: Oncolytic virus V937 in combination with PD-1 blockade therapy to target immunologically quiescent liver and colorectal cancer. (Pubmed Central) - May 15, 2024
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.
- |||||||||| VH3739937 / GSK, ViiV Healthcare
The Preclinical Profile of Maturation Inhibitor VH3739937 (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_945;
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.
- |||||||||| Cavatak (gebasaxturev) / Merck (MSD)
Preclinical, Journal, Oncolytic virus: The Effects of Mesenchymal Stem Cells Loaded with Oncolytic Coxsackievirus A21 on Mouse Models of Colorectal Cancer. (Pubmed Central) - Feb 4, 2024
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.
- |||||||||| Enrollment closed, Combination therapy: 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) - Dec 22, 2023
P1/2, N=90, Active, not recruiting,
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. Recruiting --> Active, not recruiting
- |||||||||| Cavatak (gebasaxturev) / Merck (MSD), Yervoy (ipilimumab) / Ono Pharma, BMS
P1 data, Journal, Metastases: Phase 1b study of intravenous coxsackievirus A21 (V937) and ipilimumab for patients with metastatic uveal melanoma. (Pubmed Central) - Oct 22, 2023
P1b
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. Although the combination of V937 with ipilimumab had a manageable safety profile, meaningful clinical benefit was not observed in patients with uveal melanoma and liver metastases.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Trial completion, Enrollment change, Combination therapy, Metastases: A Study of Gebasaxturev (V937) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (V937-013) (clinicaltrials.gov) - Aug 14, 2023
P1b/2, N=75, Completed,
Although the combination of V937 with ipilimumab had a manageable safety profile, meaningful clinical benefit was not observed in patients with uveal melanoma and liver metastases. Active, not recruiting --> Completed | N=185 --> 75
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Trial completion, Enrollment change, Combination therapy, Metastases: 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) - Jul 31, 2023
P2, N=85, Completed,
Active, not recruiting --> Completed | N=185 --> 75 Active, not recruiting --> Completed | N=135 --> 85
- |||||||||| Cavatak (gebasaxturev) / Merck (MSD)
Preclinical, Journal, IO biomarker: Analysis of ICAM-1 Expression on Bladder Carcinoma Cell Lines and Infectivity and Oncolysis by Coxsackie Virus A21. (Pubmed Central) - Jul 10, 2023
To date, a number of viruses have been delivered intravesically in patients and in murine models with bladder cancer and antitumour effects demonstrated. Here, we describe in vitro methods to evaluate Coxsackie virus, CVA21, as an oncolytic virus for the treatment of human bladder cancer by determining the susceptibility of bladder cancer cell lines expressing differing levels of ICAM-1 surface receptor to CVA21.
- |||||||||| Cavatak (gebasaxturev) / Merck (MSD)
Preclinical, Journal, Oncolytic virus: Glutathione affinity chromatography for the scalable purification of an oncolytic virus immunotherapy from microcarrier cell culture. (Pubmed Central) - Jul 3, 2023
Here, we describe in vitro methods to evaluate Coxsackie virus, CVA21, as an oncolytic virus for the treatment of human bladder cancer by determining the susceptibility of bladder cancer cell lines expressing differing levels of ICAM-1 surface receptor to CVA21. In this work, scalable methods were investigated for the manufacture of an oncolytic virus immunotherapy application consisting of a prototype strain of coxsackievirus A21 (CVA21) produced in adherent MRC-5 cells...The large-scale bioreactors controlled at 34
- |||||||||| Cavatak (gebasaxturev) / Merck (MSD)
Journal, IO biomarker: Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells. (Pubmed Central) - Apr 20, 2023
Significantly, CVA21 also activated natural killer (NK) cells to kill neoplastic B cells and drug-resistant B cells remained susceptible to NK cell-mediated lysis. Overall, these data reveal a dual mode of action of CVA21 against drug-resistant B cells and support the development of CVA21 for the treatment of B cell neoplasms.
- |||||||||| Oncorine (recombinant human adenovirus type 5) / Mergen Ltd., Rigvir (ECHO-7) / Rigvir Group
Preclinical, Review, Journal, Oncolytic virus: Oncolytic virus preclinical toxicology studies. (Pubmed Central) - Apr 14, 2023
This article summarizes the preclinical toxicology studies of the most well studied oncolytic viruses, including Oncorine, Talimogene laherparepvec, Cavatak, ONYX-015, teserpaturev, and Rigvir, a non-pathogenic ECHO-7 virus. It is concluded that oncolytic viruses have been shown to have low toxicity and high tolerability in preclinical toxicology studies.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Study of Gebasaxturev (V937) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (V937-013) (clinicaltrials.gov) - Feb 3, 2023
P1b/2, N=185, Active, not recruiting,
Of the combination treatments, pembro + vibo showed the most promise. Trial completion date: Jun 2024 --> Jul 2023 | Trial primary completion date: Jun 2024 --> Jul 2023
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Clinical, PK/PD data, Metastases: New #JITC article: Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), w/ or w/o pembrolizumab, in patients with advanced solid tumors https://t.co/HIxfs9o3nA @charlesrudin @MattZibelman (Twitter) - Jan 23, 2023
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Trial completion date, Trial primary completion date, Combination therapy, Metastases: 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) - Jan 20, 2023
P2, N=135, Active, not recruiting,
These results demonstrate that our method can be applied to map broad-spectrum polyclonal immune responses against intact virions and define potentially cross-reactive epitopes. Trial completion date: May 2024 --> Jun 2023 | Trial primary completion date: May 2024 --> Jun 2023
- |||||||||| Cavatak (CVA21) / Merck (MSD)
Journal, IO biomarker: Quantitation of Coxsackievirus A21 Viral Proteins in Mixtures of Empty and Full Capsids using Capillary Western. (Pubmed Central) - Dec 13, 2022
An automated and quantitative capillary western blot assay, Simple Western, was developed using these antibodies to quantify CVA21 total particles via VP1, empty particles via VP0, relative ratio of empty to full particles via VP0 and VP4, and the absolute ratio of empty to total particles via VP0 and VP1. Finally, this Simple Western method was used to support CVA21 cell culture and purification process optimization as a high-throughput, analytical tool to make rapid process decisions.
- |||||||||| Cavatak (CVA21) / Merck (MSD)
Journal: Molecular characteristics of a coxsackievirus A12 strain in Zhejiang of China, 2019. (Pubmed Central) - Oct 20, 2022
The full-length CV-A12 genome was characterized to have common recombination in P2 region and be phylogenetically related to those CV-A12 strains isolated in recent years, suggesting a continual spread in China. It warrants strengthening the routine surveillance for uncommon enterovirus serotypes, particularly on possible recombination and variation.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Study of Gebasaxturev (V937) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (V937-013) (clinicaltrials.gov) - Jul 23, 2022
P1b/2, N=185, Active, not recruiting,
Altogether, the Synthetic RNA virus platform provides an approach that enables repeat intravenous administration of viral immunotherapy. Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Jun 2024 | Trial primary completion date: Jun 2025 --> Jun 2024
- |||||||||| Cavatak (CVA21) / Merck (MSD)
Journal, Oncolytic virus: RP-UPLC method for Oncolytic Coxsackievirus Viral Protein Separation and Empty to Full Capsid Quantification. (Pubmed Central) - Jul 20, 2022
P1b/2, P2
Immunotherapy clinical drug candidate V937 is currently in phase I/II clinical trials and consists of a proprietary formulation of Coxsackievirus A21 (CVA21), which specifically infects and lyses cells with overexpressed ICAM-1 receptors in a range of tumors...We developed a sensitive and robust reverse-phase ultra-performance chromatography (RP-UPLC) method to separate, identify and quantify all five CVA21 virion proteins. Quantification of virus capsid concentration and empty/full capsid ratio was achieved with good linearity, accuracy, and precision.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Enrollment closed, Combination therapy, Metastases: 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) - May 27, 2022
P2, N=135, Active, not recruiting,
Quantification of virus capsid concentration and empty/full capsid ratio was achieved with good linearity, accuracy, and precision. Recruiting --> Active, not recruiting
- |||||||||| ONCR-788 / Oncorus, ONCR-021 / Oncorus, Cavatak (CVA21) / Merck (MSD)
Overcoming the Challenge of RNA Therapeutics for the Treatment of Cancer, Development of Lipid Nanoparticle-Formulated RNA Viral Immunotherapy (Poster Board Number: W-217; Hall D) - May 6, 2022 - Abstract #ASGCT2022ASGCT_1690;
Interestingly, the in vivo efficacy of ONCR-021 and ONCR-788 is maintained even in the presence of neutralizing antibodies against CVA21 and SVV, suggesting that administration of LNP-formulated RNA immunotherapy enables the repeated and systemic exposure of disseminated tumors to potently oncolytic viruses. These data highlight an innovative RNA therapeutic modality for the IV treatment of tumors which overcomes the limitations of other RNA-based therapeutics and supports ONCR-021 and ONCR-788 into IND-enabling studies.
- |||||||||| ONCR-021 / Oncorus
ONCR-021 as a systemic intravenous synthetic RNA virus immunotherapy for the repeat treatment of cancer (Section 24) - Mar 9, 2022 - Abstract #AACR2022AACR_2638;
Consistent with these findings, high doses levels of ONCR-021 were well-tolerated in this model. Altogether, these preclinical data support the development of ONCR-021, a novel synthetic oncolytic virus designed to overcome the challenges of repeat intravenous administration of viral immunotherapy for the treatment of disseminated cancers.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cavatak (gebasaxturev) / Merck (MSD)
Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Study of Gebasaxturev (V937) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (V937-013) (clinicaltrials.gov) - Feb 6, 2022
P1b/2, N=185, Recruiting,
Altogether, these preclinical data support the development of ONCR-021, a novel synthetic oncolytic virus designed to overcome the challenges of repeat intravenous administration of viral immunotherapy for the treatment of disseminated cancers. Trial completion date: Oct 2025 --> Sep 2026 | Trial primary completion date: Oct 2025 --> Sep 2026
- |||||||||| Cavatak (CVA21) / Merck (MSD)
Demonstration of a glutathione affinity chromatography capture step for multiple enterovirus serotypes (In-Person Room (Virtual Room)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_10241;
A novel affinity chromatography capture step utilizing immobilized reduced glutathione (GSH) was recently developed for the direct capture of Coxsackievirus A21 produced from microcarrier cell-culture with high specificity and yields...At the end of the virus production stage, viral fluid was harvested and purified using small scale high throughput chromatography columns packed with Glutathione Sepharose 4FF resin. Analysis of the elution products demonstrated that GSH affinity chromatography step maintained its mode of action for all tested enterovirus stereotypes and delivered concentrated and purified viruses.
- |||||||||| Cavatak (CVA21) / Merck (MSD)
Journal, Oncolytic virus: SEC coupled with in-line multiple detectors for the characterization of an oncolytic Coxsackievirus. (Pubmed Central) - Jan 14, 2022
Using a 4-in-1 combination of multi-detectors (UV, refractive index, dynamic and static light scattering), we demonstrate the use of SEC for the quantification of the virus particle count, the determination of virus size (molecular weight and hydrodynamic diameter), and the characterization of virus purity by assessing empty-to-full capsid ratios. Through a SEC analysis of stressed V937 samples, we propose CVA21 thermal degradation pathways that result in genome release and particle aggregation.
- |||||||||| Cavatak (CVA21) / Merck (MSD)
Clinical, Journal: Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy. (Pubmed Central) - Sep 11, 2021
We find that prior exposure to CVA21 does not dramatically affect tumor responses, nor does it alter overall survival. Our results suggest that prior exposure to coxsackievirus is not a critical determinant of patient selection for IT CVA21 interventions.
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