- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
[VIRTUAL] Integrating Oncolytic Viruses into Combination Therapy for Cancer () - Aug 18, 2020 - Abstract #IOS2020IOS_126;
We have recently shown potent synergy between MEK inhibition and T-VEC in preclinical tumor models. In this presentation, emerging data on how to optimize anti-tumor immunity with OVs will be reviewed.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Journal: Integrative functional genomics decodes herpes simplex virus 1. (Pubmed Central) - Aug 11, 2020
This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic...We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Journal: Intratumoural immunotherapies in oncology. (Pubmed Central) - Aug 2, 2020
However, intratumoural therapies are moving to other tumour types and advances in endoscopic and interventional radiological techniques are allowing these agents to be injected into visceral lesions. This review provides an overview of the current status of intratumoural therapies in oncology, as well as future directions regarding therapeutic niches and appropriate trial design for intratumoural agents.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Opdivo (nivolumab) / BMS, Yervoy (ipilimumab) / BMS
Trial completion date, Trial primary completion date, Tumor mutational burden: Glaspy BMS CA209-9ET Breast: Ipilimumab, Nivolumab, and Talimogene Laherparepvec Before Surgery in Treating Participants With Localized, Triple-Negative or Estrogen Receptor Positive, HER2 Negative Breast Cancer-deleted (clinicaltrials.gov) - Jul 22, 2020
P1, N=20, Recruiting,
Funding: Has not received any funding. Trial completion date: Jul 2021 --> Jul 2022 | Trial primary completion date: Jul 2020 --> Jul 2021
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Enrollment closed, Enrollment change, Metastases: Study of T-VEC in Locally Advanced Cutaneous Angiosarcoma (clinicaltrials.gov) - Jul 20, 2020
P2, N=4, Active, not recruiting,
Trial completion date: Jul 2021 --> Jul 2022 | Trial primary completion date: Jul 2020 --> Jul 2021 Recruiting --> Active, not recruiting | N=13 --> 4
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Review, Journal, Oncolytic Virus: Recent advances in oncolytic virus-based cancer therapy. (Pubmed Central) - Jul 19, 2020
The effectiveness of OV therapy was initially highlighted by the clinical use of the genetically modified herpes virus, talimogene laherparepvec, for melanoma therapy...In this review, we highlight the recent advances in OV therapy for a range of human cancers in in vitro and in in vivo animal studies. We further discuss the future of OVs as a therapeutic strategy for a range of life-threatening cancers.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Keytruda (pembrolizumab) / Merck (MSD)
Trial completion date, Trial primary completion date, Tumor mutational burden, IO biomarker, Metastases: S1607: Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma (clinicaltrials.gov) - Jul 15, 2020
P2, N=47, Recruiting,
We further discuss the future of OVs as a therapeutic strategy for a range of life-threatening cancers. Trial completion date: Jun 2020 --> Jun 2023 | Trial primary completion date: Jun 2020 --> Jun 2023
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Clinical, Review, Journal, Oncolytic Virus: Optimizing Oncolytic Viral Design to Enhance Antitumor Efficacy: Progress and Challenges. (Pubmed Central) - Jul 3, 2020
The field of oncolytic virotherapy has seen remarkable advancements in last two decades, leading to approval of the first oncolytic immuno-virotherapy, Talimogene Laherparepvec, for the treatment of melanoma...Other transgenes used to arm oncolytic viruses include those with the potential to favorably modulate tumor stroma, making it possible to image the virus distribution and increase its suitability for combination with other therapeutics. This review will detail the progress made in arming oncolytic viruses with a focus on immune-modulatory transgenes, and will discuss the challenges that need to be addressed for more armed oncolytic viruses to find widespread clinical use.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Clinical, Journal, Oncolytic Virus: Oncolytic virotherapy for malignant tumor: current clinical status. (Pubmed Central) - Jun 19, 2020
However, the mechanisms of virus interaction with tumor and immune system haven't been clearly elucidated and there are still not any "gold standards" for instructions of virotherapy in clinical trials. This Review collected the recent clinical trials data from 2005 to summarize the basic oncolytic viruses biology, describes the application in recent clinical trials and discusses the challenges in the application of oncolytic viruses in clinical trials.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Review, Journal, Oncolytic Virus: From threat to cure: understanding of virus-induced cell death leads to highly immunogenic oncolytic influenza viruses. (Pubmed Central) - Jun 17, 2020
The first oncolytic virus, Talimogene laherparepvec (T-VEC), based on herpes simplex virus 1 (HSV-1), was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2015...We discuss strategies for targeting viral replication to cancerous lesions and arming them with immunogenic transgenes. We furthermore describe which modes of cell death are induced by influenza A virus infection and how these insights may be utilized to optimize influenza A virus-based oncolytic virus design.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Opdivo (nivolumab) / BMS
Enrollment open, Enrollment change, Trial completion date, Trial primary completion date, PD(L)-1 Biomarker, IO biomarker: NCI#10057: Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers (clinicaltrials.gov) - Jun 11, 2020
P2, N=100, Recruiting,
Recruiting --> Active, not recruiting | N=36 --> 11 Suspended --> Recruiting | N=68 --> 100 | Trial completion date: Jun 2020 --> Jun 2021 | Trial primary completion date: Jun 2020 --> Jun 2021
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
[VIRTUAL] Tumor Response Evaluation Criteria for Intratumoral Therapy (Virtual Meeting II: All Session Times Are U.S. EDT) - Jun 11, 2020 - Abstract #AACRII2020AACR-II_5606;
Virtual Meeting sessions are available through the AACR website: aacr.org/vm2 In October 2015, the US FDA approved talimogene laherparepvec (T-vec), the first oncolytic virus therapy and the first intratumoral therapy, for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery...discuss the impact of imaging modalities on the response evaluation criteria; and 5. discuss response criteria for intratumoral immunotherapy in solid tumors (itRECIST) and its potential advantages and challenges.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Yervoy (ipilimumab) / Ono Pharma, BMS
Journal, Combination therapy: Patterns of response with talimogene laherparepvec in combination with ipilimumab or ipilimumab alone in metastatic unresectable melanoma. (Pubmed Central) - Jun 8, 2020
P1b/2
Eight responders (combination, n = 7 [18.4%]; ipilimumab, n = 1 [5.6%]) had pseudo-progression; most occurred by week 12 and were caused by an increase in existing lesions. These data reinforce use of T-VEC through initial progression when combined with checkpoint inhibitors.Trial Registration NCT01740297 (ClinicalTrials.gov; date of registration, December 4, 2012); 2012-000307-32 (ClinicalTrialsRegister.eu; date of registration, May 13, 2014).
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Retrospective data, Review, Journal, Oncolytic Virus: Efficacy and Safety of Oncolytic Viruses in Randomized Controlled Trials: A Systematic Review and Meta-Analysis. (Pubmed Central) - Jun 7, 2020
Among the five OVs investigated in RCTs, only talimogene laherparepvec (T-VEC) effectively prolonged the OS of patients (hazard ratio (HR), 0.79; 95% CI: 0.63-0.99; p = 0.04)...This review offers a reference for fundamental research and clinical treatment of oncolytic viruses. Further randomized controlled trials are needed to verify these results.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Afinitor (everolimus) / Novartis
Preclinical, Journal, IO Biomarker: The Oncolytic Herpes Simplex Virus Talimogene Laherparepvec Shows Promising Efficacy in Neuroendocrine Cancer Cell Lines. (Pubmed Central) - May 31, 2020
Moreover, virostatic effects of ganciclovir (GCV) on replication of T-VEC were assessed and electron microscopic pictures were taken to comprehend viral envelopment and details of the replication cycle of T-VEC in human neuroendocrine cancer...On the other hand, GCV was shown to be able to limit replication of T-VEC, thus establishing an important safety feature for future treatments of NET/NEC patients. Taken together, T-VEC opens up a promising novel treatment option for NET/NEC patients, warranting its further preclinical and clinical development.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Provenge (sipuleucel-T) / Bausch Health
Review, Journal: Cancer Vaccines. (Pubmed Central) - May 23, 2020
Prior clinical trials have shown that vaccines are generally well tolerated, exhibit unique kinetics, can target tumor neoantigens, and induce antigen cascade. Ongoing clinical trials seek to improve vaccine efficacy either by targeting novel antigens or by combining vaccines with standard-of-care therapies or other immune therapies.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Trial completion date, Trial primary completion date: Study of TVEC in Patients With Cutaneous Squamous Cell Cancer (clinicaltrials.gov) - May 19, 2020
P2, N=28, Recruiting,
Recruiting --> Active, not recruiting Trial completion date: Sep 2020 --> Sep 2021 | Trial primary completion date: Mar 2020 --> Mar 2021
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
OnxoVEXmGM-CSF promotes systemic response to PD-L1 /PD-1 blockade in multiple mouse syngeneic tumor models (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_692;
Together, these data reveal that OncoVEXmGM-CSF treatmentcan cause direct tumor lysis along with the potentiation of an adaptive, systemic T cell-mediated anti-tumor immune response that can be enhanced by the addition of PD-L1/PD-1. Our study provides a strong rationale for the ongoing clinical evaluation of the combination of T-VEC and PD1-/PD-L1-targeted therapy in cancer patients.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, ONCOS-102 / Targovax
Next generation Oncos oncolytic adenovirus with novel anti-cancer double-transgenes shows synergistic anticancer effect in melanoma mouse model (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_2961;
One example is ONCOS-102, an adenovirus serotype 5/3 chimera expressing GM-CSF as a transgene, which recently reported 33% ORR in advanced anti-PD1 refractory melanoma.Genetically engineered OVs can be armed with different co-stimulatory molecules in order to boost the anti-tumour immune responses...The double transgenes were shown to act synergistically in vivo, in line with the design hypotheses and proposed mode of action to induce cell lysis and prevent tumor growth. Moreover, the vectors were able to increase tumor infiltration of various immune subsets including CD4+, CD8+, CD8+ expressing PD1+ or CD8+ expressing Granzyme B T cells and reduction of regulatory T-cells and MDSC in the tumour microenvironment, suggesting an ability to prime immune-suppressive tumors to better respond to immunotherapy.These encouraging preclinical findings will be further investigated to elucidate the mode of action and perform toxicological studies to bring ONCOS-210 and ONCOS-212 towards clinical testing.
- |||||||||| ontorpacept intratumoral (TTI 621 intratumoral) / Pfizer
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides (clinicaltrials.gov) - May 14, 2020
P1, N=56, Terminated,
Transgene and BioInvent are preparing CTA and IND filings for a multicentre clinical trial targeting injectable superficial tumors. N=240 --> 56 | Trial completion date: Dec 2019 --> Mar 2020 | Recruiting --> Terminated | Trial primary completion date: Dec 2019 --> Mar 2020
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Review, Journal: The Future of Immunotherapy in the Treatment of Cancer. (Pubmed Central) - Apr 30, 2020
Nurses play a pivotal role in the care of the cancer patient across the continuum. With the unique toxicities associated with immunotherapy, it is essential that nurses be keenly aware of all aspects of management, from physical to financial care.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Clinical, Journal, IO biomarker: Enhancing Antitumor Efficacy of Heavily Vascularized Tumors by RAMBO Virus through Decreased Tumor Endothelial Cell Activation. (Pubmed Central) - Apr 30, 2020
P2
Numerous studies are also being conducted regarding the effects of oncolytic viruses, including Imlygic, an FDA approved oncolytic herpes simplex virus-1 (oHSV) for the treatment of highly vascularized tumors such as Kaposi sarcoma (NCT04065152), and brain tumors...In addition, histological analysis of RAMBO-treated tumor tissues revealed large areas of necrosis and a statistically significant reduction in microvessel density (MVD). This study provides strong preclinical evidence of the therapeutic benefit for the use of RAMBO virus as a treatment option for highly vascularized tumors.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Virally delivered cytokine therapy drives immune equilibrium in melanoma (Board Number: P1212) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_2638;
Although a modified, replicating herpes simplex virus (HSV) encoding GM-CSF was FDA-approved for the treatment of melanoma (T-VEC), which was revolutionary for the field of oncolytic virotherapy, there are several areas for improvement...We have profiled the immune response induced by d106S-IL12 at separate time points, identifying several points of possible intervention, including blockade of innate inflammatory cytokines IL-1β, TNFα and IL-6. Indeed, blockade of each of these inflammatory cytokines provides a boost to the response initiated by d106S-IL12, which we have further profiled with single-cell RNA-sequencing.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Clinical, Journal: Oncolytic herpes simplex virus therapy for malignant glioma: Current approaches to successful clinical application. (Pubmed Central) - Apr 22, 2020
With the approval of talimogene laherparepvec (T-VEC) for advanced malignant melanoma, virotherapy using oncolytic herpes simplex virus (oHSV) is now emerging as a viable therapeutic option for cancer patients, including malignant gliomas...Expert Opinion: Current strategies to improve the efficacy of oHSV therapy include engineering new viruses, modulation of innate and adaptive immune responses, combination with other treatments, and developing new oHSV delivery. All of these could rapidly be translated into clinical investigations, following several clinical trials that are currently ongoing.
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