Ofranergene obadenovec (VB-111) in platinum-resistant ovarian cancer; favorable response rates in a phase I/II study are associated with an immunotherapeutic effect

Arend, Rebecca C.; Beer, Hannah; Cohen, Yaël; Berlin, Suzanne; Birrer, Michael J.; Campos, Susana M.; Minei, Tamar Rachmilewitz; Harats, Dror; Wall, Jaclyn; Foxall, McKenzie E.; Penson, Richard T.

doi:10.1016/j.ygyno.2020.02.034

Cited by 20 publications

(15 citation statements)

References 14 publications

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“…Recombinant unarmed adenoviruses demonstrate low toxicity (Grade 1–2) and impressive oncolytic potential which can be boosted by additional expression of immunostimulatory molecules (IFN-gamma, GM-CSF) or p53 (rAd-p53) [ 42 , 43 , 44 ]. More than 400 patients have been treated with rAd-p53, mainly in combination with chemotherapy [ 45 ], radiotherapy [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ] and tumor resection [ 54 ] with various efficacy. Thus the overall response rate for combined treatment with cisplatin of malignant pleural effusion caused by lung cancer has reached an encouraging 82% [ 50 ].…”

Section: Oncolytic Viruses In Clinical Trialsmentioning

confidence: 99%

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes

Malogolovkin

Gasanov

Egorov

et al. 2021

Viruses

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Recent cancer immunotherapy breakthroughs have fundamentally changed oncology and revived the fading hope for a cancer cure. The immune checkpoint inhibitors (ICI) became an indispensable tool for the treatment of many malignant tumors. Alongside ICI, the application of oncolytic viruses in clinical trials is demonstrating encouraging outcomes. Dozens of combinations of oncolytic viruses with conventional radiotherapy and chemotherapy are widely used or studied, but it seems quite complicated to highlight the most effective combinations. Our review summarizes the results of clinical trials evaluating oncolytic viruses with or without genetic alterations in combination with immune checkpoint blockade, cytokines, antigens and other oncolytic viruses as well. This review is focused on the efficacy and safety of virotherapy and the most promising combinations based on the published clinical data, rather than presenting all oncolytic virus variations, which are discussed in comprehensive literature reviews. We briefly revise the research landscape of oncolytic viruses and discuss future perspectives in virus immunotherapy, in order to provide an insight for novel strategies of cancer treatment.

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Section: Oncolytic Viruses In Clinical Trialsmentioning

confidence: 99%

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes

Malogolovkin

Gasanov

Egorov

et al. 2021

Viruses

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“…A trend for improved OS was seen in patients with a CA-125 decrease of at least 50% (808 days vs. 351 days p=0.067), and in patiens with post treatment fever (808 days vs. 479 days in patients (p=0.27). Post-treatment tumor specimens demonstrated infiltration of cytotoxic CD8 T-cells in regions of apoptotic cancer cells, which supports the VB-111 immunologic mechanism of action and its ability to make tumors more immunogenic [5]. Following these encouraging results, the OVAL study (NCT03398655) was initiated.…”

Section: Ofranergene Obadenovec (Vb-111)mentioning

confidence: 71%

Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer

Arend

Monk

Herzog

et al. 2021

Gynecologic Oncology

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OVAL is a Phase III trial using paclitaxel and VB-111 in recurrent ovarian cancer • VB-111 has a dual mechanism targeting tumor vasculature and anti-tumor immunity • CA-125 response in the VB-111 treated arm met the pre-specified interim criterion • Assuming balanced randomization, the response in the VB-111 arm was at least 58% • The OVAL study has been recommended to continue enrollment as planned

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“…This transgene is restricted however to angiogenic endothelial cells which nearly exclusively have an activated pre-proendothelin 1 (PPE-1)–3x promoter ( 63 ). Initiation of this therapy has shown to result in dramatic infiltration of CD8+ T cells in tumor tissue with subsequent cell apoptosis, which likely results dually from pathways downstream of chimeric death receptor in addition to immunogenic viral epitopes that stimulate immune targeting ( 134 ). While a phase III trial failed to demonstrate survival benefit of VB-111, the patients enrolled here did not receive a ‘priming’ dose of VB-111 that may prove necessary in synergistic success with bevacizumab, as demonstrated with the good results in prior phase II study that used such a ‘priming’ dose in the study design ( 135 ).…”

Section: Synergy In Immunotherapy and Antiangiogenic Agents In Gbmmentioning

confidence: 99%

Interactions Between Anti-Angiogenic Therapy and Immunotherapy in Glioblastoma

2022

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Glioblastoma is the most aggressive brain tumor with a median survival ranging from 6.2 to 16.7 months. The complex interactions between the tumor and the cells of tumor microenvironment leads to tumor evolution which ultimately results in treatment failure. Immunotherapy has shown great potential in the treatment of solid tumors but has been less effective in treating glioblastoma. Failure of immunotherapy in glioblastoma has been attributed to low T-cell infiltration in glioblastoma and dysfunction of the T-cells that are present in the glioblastoma microenvironment. Recent advances in single-cell sequencing have increased our understanding of the transcriptional changes in the tumor microenvironment pre and post-treatment. Another treatment modality targeting the tumor microenvironment that has failed in glioblastoma has been anti-angiogenic therapy such as the VEGF neutralizing antibody bevacizumab, which did not improve survival in randomized clinical trials. Interestingly, the immunosuppressed microenvironment and abnormal vasculature of glioblastoma interact in ways that suggest the potential for synergy between these two therapeutic modalities that have failed individually. Abnormal tumor vasculature has been associated with immune evasion and the creation of an immunosuppressive microenvironment, suggesting that inhibiting pro-angiogenic factors like VEGF can increase infiltration of effector immune cells into the tumor microenvironment. Remodeling of the tumor vasculature by inhibiting VEGFR2 has also been shown to improve the efficacy of PDL1 cancer immunotherapy in mouse models of different cancers. In this review, we discuss the recent developments in our understanding of the glioblastoma tumor microenvironment specially the tumor vasculature and its interactions with the immune cells, and opportunities to target these interactions therapeutically. Combining anti-angiogenic and immunotherapy in glioblastoma has the potential to unlock these therapeutic modalities and impact the survival of patients with this devastating cancer.

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Ofranergene obadenovec (VB-111) in platinum-resistant ovarian cancer; favorable response rates in a phase I/II study are associated with an immunotherapeutic effect

Cited by 20 publications

References 14 publications

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes

Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer

Interactions Between Anti-Angiogenic Therapy and Immunotherapy in Glioblastoma

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