- |||||||||| Cytovene (ganciclovir) / Roche, ProstAtak (aglatimagene besadenovec) / Candel Therap, Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Clinical, Review, Journal, Gene therapy: Gene therapy for people with hepatocellular carcinoma. (Pubmed Central) - Jun 5, 2024
The impact of gene therapy on adverse events needs to be investigated further. Evidence on the effect of gene therapy on health-related quality of life is lacking.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Vascularized gastric cancer 3D co-culture model using a microphysiological system as an oncolytic virus testing platform (Section 6) - Mar 5, 2024 - Abstract #AACR2024AACR_8578;
Our findings suggest the potential utility of plasma cytokine and chemokine profiles in clinical benefits of mRCC patient to the combination of Pexa-Vec and cemiplimab, thereby aiding in future personalized treatment approaches. JX-594 had an inhibitory effect on tumor-induced angiogenesis in our vascularized gastric cancer in vitro 3D human cell co-culture model, demonstrating the utility of the platform as a tool to interrogate the effects of an oncolytic virus on both tumor cell killing and tumor-induced angiogenesis.
- |||||||||| Bavencio (avelumab) / EMD Serono, Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Biomarker, P2 data, Journal, Oncolytic virus, Tumor microenvironment, PD(L)-1 Biomarker, IO biomarker: Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide. (Pubmed Central) - Feb 25, 2024
Analysis of sequential tissue biopsies and plasma samples revealed an increase in CD8 density and upregulation of immune-related protein biomarkers, including CXCL10.Intra-tumoral administration of JX-594 in combination with cyclophosphamide and avelumab is safe and capable of modulating the TME in cold STS. However, the limited efficacy observed warrants further research to define the therapeutic potential of oncolytic viruses, particularly in relation to specific histological subtypes of STS.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Trial completion, Combination therapy, Oncolytic virus, Checkpoint inhibition: A Phase I/II Study of Pexa-Vec Oncolytic Virus in Combination With Immune Checkpoint Inhibition in Refractory Colorectal Cancer (clinicaltrials.gov) - Oct 24, 2023
P1/2, N=34, Completed,
However, the limited efficacy observed warrants further research to define the therapeutic potential of oncolytic viruses, particularly in relation to specific histological subtypes of STS. Active, not recruiting --> Completed
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Targeting immunosuppressive adenosine to enhance vaccinia virus renal cancer oncolysis in vivo (Section 44; Poster Board #8) - Mar 14, 2023 - Abstract #AACR2023AACR_8182;
MJX-594 combination with A2AR and A2BR inhibition safely and significantly improves renal cancer oncolysis and tumor control in vivo. Our studies uncover a novel, translationally relevant strategy to improve OV efficacy in vivo, in RCC and other cancers.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Synergistic antitumor effect of oncolytic virus and cytotoxic chemotherapy in gastric cancer (Section 14; Poster Board #21) - Mar 14, 2023 - Abstract #AACR2023AACR_4907;
This study shows combination synergism and provides a promising approach to combination therapy with an oncolytic virus on gastric cancer. For future research, additional studies on other gastric cancer cell lines and investigation of mechanisms are needed.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Anti-PD1 plus oncolytic virus as first-line treatment option for metastatic renal cell carcinomas. (On Demand | Level 1, West Hall; Poster Board No. H7) - Jan 10, 2023 - Abstract #ASCOGU2023ASCO_GU_803;
JX-594 plus anti-PD1 effectively reduced primary tumors and metastatic burdens similar to ICI combination therapy. Furthermore, imAEs significantly decreased in JX-594 plus anti-PD1 group, suggesting the potential benefit of JX-594 plus anti-PD1 for reserving ICI induced toxicities, especially by anti-CTLA-4.
- |||||||||| SVV-001 / Seneca Therap, Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Review, Journal, Oncolytic virus: Progress of oncolytic virotherapy for neuroblastoma. (Pubmed Central) - Dec 6, 2022
Furthermore, clinical trials on some OVs (Celyvir, Pexa-Vec (JX-594) and Seneca Valley Virus (NTX-010)) have reported great results. This review summarizes the latest evidence in the therapeutic application of OVs in NB, including those generated in cell lines, animal models and clinical trials.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene, Yervoy (ipilimumab) / Ono Pharma, BMS
Addition of oncolytic virus is as effective as addition of cytoreductive nephrectomy to the first-line treatment of anti-PD-1/anti-CTLA-4 antibodies in the murine metastatic renal cell carcinoma model (Poster Area, Hall 4) - Jul 28, 2022 - Abstract #ESMO2022ESMO_2063;
Increased expression of PD-L1 by JX-594 supported the rationale for combining with ipi/nivo, and anti-PD-1 modulated the TIME to tumor-suppressing environment which complemented the therapeutic effects of JX-594. Furthermore, JX-594 has successfully demonstrated it as the promising alternative therapy option to CN, without concern for surgical morbidity by the CN.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial completion, Trial primary completion date, Combination therapy, Metastases: ISI-JX: Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors. (clinicaltrials.gov) - Jul 25, 2022
P1, N=22, Completed,
Furthermore, JX-594 has successfully demonstrated it as the promising alternative therapy option to CN, without concern for surgical morbidity by the CN. Active, not recruiting --> Completed | Trial primary completion date: Jan 2022 --> Apr 2022
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial primary completion date, Combination therapy, Metastases: ISI-JX: Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors. (clinicaltrials.gov) - Jul 23, 2022
P1, N=22, Active, not recruiting,
Active, not recruiting --> Completed | Trial primary completion date: Jan 2022 --> Apr 2022 Trial primary completion date: Jun 2022 --> Jan 2022
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Journal, Oncolytic virus: Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anti-Cancer Immunity in Patients. (Pubmed Central) - Jun 8, 2022
Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials...In the two patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of pre-surgical oncolytic vaccinia virus-based therapies to stimulate anti-cancer immunity and increase the chances to cure patients with cancer.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Journal, Oncolytic virus, IO biomarker: Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients. (Pubmed Central) - May 15, 2022
This differential baseline immunological profile accurately predicted the subsequent response to Pexa-Vec and may, therefore, enable the development of predictive biomarkers for Pexa-Vec and OV therapies more widely. If confirmed in larger clinical trials, these immunological biomarkers may enable a personalised approach, whereby patients with an exhausted baseline immune profile are treated with immune checkpoint blockade, with the aim of reversing immune exhaustion, prior to or alongside OV therapy.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Journal, Oncolytic virus: Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8 T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy. (Pubmed Central) - Apr 24, 2022
mJX-594 treatment increased T cell factor 1-positive stem-like T cells among cancer-specific CD8 T cells, and anti-PD-1 combination treatment further increased proliferation of these cells, which was important for therapeutic efficacy. The presence of functional cancer-specific CD8 T cells in the spleen and bone marrow for an extended period, which proliferated upon encountering cancer antigen-loaded splenic dendritic cells, further indicated that long-term durable anticancer immunity was elicited by oncolytic VACV.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial completion date, Trial primary completion date, Combination therapy, Metastases: ISI-JX: Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors. (clinicaltrials.gov) - Mar 24, 2022
P1, N=22, Active, not recruiting,
N=40 --> 54 Trial completion date: Mar 2022 --> Sep 2022 | Trial primary completion date: Dec 2021 --> Jun 2022
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
In vitro cellular and molecular effects of oncolytic vaccinia virus in clear and non-clear cell renal cell carcinoma (Section 24) - Mar 9, 2022 - Abstract #AACR2022AACR_5411;
P1b/2a
In particular, the proteins related to cell cycle (Wee1, Cdc25c, CHK1/2, and Cyclin B1) and Akt signaling (PI3K, mTOR, Rictor and FOXO), MAPK signaling (JAK2, PAK1, FAK and MEK1) were down regulated, while proteins involved in apoptosis and necrosis were upregulated. In summary, our studies show that human and murine renal cancer cells are permissive to infection and replication by JX-594 and mJX-594, which induce potent oncolytic effects in clear and non-clear cell RCC, effects associated with significant modulation of RCC pathways associated with cell cycle, proliferation, and survival and stress responses.
- |||||||||| Oncorine (recombinant human adenovirus type 5) / Mergen Ltd., canerpaturev (TBI-1401) / Takara
Retrospective data, Review, Journal, Oncolytic virus: The efficacy and safety of oncolytic viruses in the treatment of intermediate to advanced solid tumors: a systematic review and meta-analysis. (Pubmed Central) - Feb 5, 2022
A total of 22 studies involving 3,996 patients were included in this analysis, including 13 H101 studies, 5 T-VEC studies, 2 Pexa-Vec studies, 1 HF10 study and 1 Reolysin study...The adverse events (AEs) associated with the other OVs mainly included fever, nausea and vomiting, leukopenia, and hypotension. OVs are effective and well tolerated for the treatment of intermediate to advanced solid cancer and represent a promising therapeutic approach for solid cancers.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Journal, Oncolytic virus, Checkpoint inhibition: Oncolytic vaccinia virus injected intravenously sensitizes pancreatic neuroendocrine tumors and metastases to immune checkpoint blockade. (Pubmed Central) - Feb 5, 2022
This study determined the influence of intravenous (i.v.) oncolytic vaccinia virus mpJX-594 (mpJX) on antitumor activity of anti-programmed death receptor-1 antibody (aPD1) in functional and metastatic pancreatic neuroendocrine tumors (PanNETs)...Reduction of tumor insulin secretion from functional PanNETs prolonged survival, and anti-metastatic actions on aggressive PanNETs reduced the metastatic burden to less than before treatment. The findings support the efficacy of the vaccinia virus with aPD1 for functional and metastatic PanNETs.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene, Yervoy (ipilimumab) / Ono Pharma, BMS
Enrollment closed, Enrollment change, Combination therapy, Metastases: ISI-JX: Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors. (clinicaltrials.gov) - Nov 17, 2021
P1, N=22, Active, not recruiting,
Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting | N=66 --> 22
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Review, Journal: Kinase inhibitors with viral oncolysis: Unmasking pharmacoviral approaches for cancer therapy. (Pubmed Central) - Sep 15, 2021
While this trial failed to show any benefits over Sorafenib monotherapy in patients with advanced liver cancer, several pre-clinical studies demonstrate that targeting kinases combined with oncolytic viruses have synergistic effects highlighting this strategy as a unique avenue to cancer therapy. Herein, we review the combinations of oncolytic viruses with kinase inhibitors reported in the literature and discuss the clinical opportunities that represent these pharmacoviral approaches.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Enrollment change, Trial completion date, Trial termination, Oncolytic virus, Metastases: A Trial to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - Aug 18, 2021
P1/2, N=14, Terminated,
Herein, we review the combinations of oncolytic viruses with kinase inhibitors reported in the literature and discuss the clinical opportunities that represent these pharmacoviral approaches. N=30 --> 14 | Trial completion date: Sep 2020 --> Feb 2021 | Active, not recruiting --> Terminated; The decision was taken to stop prematurely the trial due to the failure of Pexa-Vec and nivolumab in their respective pivotal trials (i.e., PHOCUS and CheckMate 459).
- |||||||||| dimethyl fumarate / Generic mfg.
Repurposing of Kreb’s cycle-derived metabolites as antiviral agents and oncolytic virus sensitizers (Room: B313b - B314) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_3243;
Pre-treatment of 4T1 aggressive murine breast cancer cells and 786-O human renal carcinoma cells with 4-OI markedly reduced the replicative properties of HSV-1 g34.5 and Vaccinia Virus JX-594 but dramatically enhanced VSVDM51 infectivity and oncolytic activity in vitro. Altogether, our data suggest that endogenous metabolites are plausible broad-spectrum anti-viral agents that could be used in the treatment of existing or newly emerging viral infections but at the same time can also serve the purpose of virus boosters in oncolytic virotherapy treatment of cancer.
- |||||||||| Review, Journal: Intratumoral Immunotherapy-Update 2019. (Pubmed Central) - Jun 22, 2021
In 2019, a multitude of intratumoral immunotherapies with varied mechanisms of action, including nononcolytic viral therapies such as PV-10 and toll-like receptor 9 agonists and oncolytic viral therapies such as CAVATAK, Pexa-Vec, and HF10, have been extensively evaluated in clinical trials and demonstrated promising antitumor activity with tolerable toxicities in melanoma and other solid tumor types...This review summarizes current knowledge on intratumoral therapies, a novel modality with increased utility in cancer treatment, and T-VEC, the only U.S. FDA-approved oncolytic viral therapy, for medical oncologists. This review evaluates approaches to incorporate T-VEC into daily practice to offer the possibility of response in selected melanoma patients with manageable adverse events as compared with other available immunotherapies.
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
[VIRTUAL] Intensified Production of Vaccinia-Based Oncolytics in the High Density Cell Respirator (HDCR) Bioreactor Improves Vaccine Logistics and Economics () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_826;
Many promising vectors, including those based on vaccinia virus (e.g. CF33, JX-594/Pexa-Vec) are still produced using flask-based culture due to the cost, effort, and uncertainty involved in adapting to stirred-tank or perfusion processes...The straightforward adaptation of CF33 virus production from a flask-based to a high yield, intensified process highlights the logistical and economical advantage of the HDCR platform for oncolytics. Table 1: Production metrics for CF33 virus produced in HDCR bioreactor.Virus StrainCrude Yield (PFU/Run)Specific Yield (PFU/Cell)Media Usage (Liters)Cost Per 1010 Purified PFUCF33-hNIS-αPDL16E102810.5402CF33-mCD19t2.6E1113010.9275CF33-tk2.8E101810.6540
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Phase classification, Combination therapy, Metastases: JX594-REN026: A Study of Recombinant Vaccinia Virus in Combination With Cemiplimab for Renal Cell Carcinoma (clinicaltrials.gov) - Jan 19, 2021
P1b/2a, N=117, Recruiting,
Table 1: Production metrics for CF33 virus produced in HDCR bioreactor.Virus StrainCrude Yield (PFU/Run)Specific Yield (PFU/Cell)Media Usage (Liters)Cost Per 1010 Purified PFUCF33-hNIS-αPDL16E102810.5402CF33-mCD19t2.6E1113010.9275CF33-tk2.8E101810.6540 Phase classification: P1b --> P1b/2a
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Trial primary completion date, Combination therapy, Oncolytic virus, Checkpoint inhibition, PD(L)-1 Biomarker: A Phase I/II Study of Pexa-Vec Oncolytic Virus in Combination With Immune Checkpoint Inhibition in Refractory Colorectal Cancer (clinicaltrials.gov) - Jan 15, 2021
P1/2, N=34, Active, not recruiting,
Phase classification: P1b --> P1b/2a Trial primary completion date: Dec 2020 --> Sep 2020
- |||||||||| Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Transgene
Enrollment change, Combination therapy, Oncolytic virus, Checkpoint inhibition, PD(L)-1 Biomarker: A Phase I/II Study of Pexa-Vec Oncolytic Virus in Combination With Immune Checkpoint Inhibition in Refractory Colorectal Cancer (clinicaltrials.gov) - Dec 10, 2020
P1/2, N=34, Active, not recruiting,
Active, not recruiting --> Completed | Trial completion date: Dec 2020 --> Jul 2020 | Trial primary completion date: Dec 2020 --> Jul 2020 N=23 --> 34
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