This is a Phase 2 study designed to determine the preliminary anti-tumor activity and confirm the safety of VV1 in combination with cemiplimab. The study will enroll patients with three distinct separate tumor cohorts. The cancers types are colorectal, head and neck carcinoma, and melanoma that are progressing on CPI treatment.

开始日期2020-04-24

申办/合作机构

Vyriad, Inc.初创企业

[+1]

NCT03647163 / Recruiting临床1/2期

Phase 1-2 Trial of Systemically Administered VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Selected Solid Tumors

The safety run-in portion of this study is designed to identify the optimal dose of VSV-IFNβ-NIS in combination with pembrolizumab in patients with solid tumors and follows the 3+3 design. The expansion portion will use one-sample binomial designs to assess the efficacy of the combination in patients with refractory NSCLC or NEC. The optimal dose (RP2D) determined in the dose escalation portion of the trial will be used for the expansion portion. The study has been conducted with a dose of 1.7 × 1010 as the recommended phase II dose in an expansion cohort of 10 patients with NSCLC. However, current data suggests that VSV-IFNβ-NIS doses of up to 1.7 × 1011 is safe and likely more efficacious. Thus, this study will test a second VSV-IFNβ-NIS dose level, 1.0x1011 TCID50. A safety assessment will be carried out after 3 patients are enrolled. If this dose schedule is well tolerated and virus PK are not negatively impacted, both the NSCLC and NEC expansion cohorts will open using this dose schedule. If 2 of the first 3 patients or 2 of the first 6 patients experience a DLT, the dose will be de-escalated to 5 x 1010. The safety run-in/dose escalation portion of this study is expected to require a minimum of 3 patients and a maximum of 18 patients (6 patients per dose level). The expansion portion of this study is expected to require a minimum of 10 per cohort. The NSCLC and NEC patients enrolled at the identified optimal dose in the dose escalation cohort would be included in the dose expansion cohort if they are evaluable for the primary endpoint in the expansion portion (4 dose escalation patients at the optimal dose are expected to roll over to the expansion). Therefore, the overall sample size will be a maximum of 40 patients.

开始日期2019-04-09

申办/合作机构

Vyriad, Inc.初创企业

[+1]

NCT03120624 / Active, not recruiting临床1期IIT

Phase I Trial of Intravenous Administration of Vesicular Stomatitis Virus Genetically Engineered to Express Thyroidal Sodium Iodide Symporter (NIS) and Human Interferon Beta (hIFNb), in Patients With Metastatic or Recurrent Endometrial Cancer

This phase I trial studies the side effects and best dose of vesicular stomatitis virus-human interferon beta-sodium iodide symporter (VSV-hIFNbeta-NIS) with or without ruxolitinib phosphate in treating patients with stage IV endometrial cancer or endometrial cancer that has come back. The study virus, VSV-hIFNbeta-NIS, has been changed so that it has restricted ability to spread to tumor cells and not to healthy cells. It also contains a gene for a protein, NIS, which helps the body concentrate iodine making it possible to track where the virus goes. VSV-hIFNbeta-NIS may be able to kill tumor cells without damaging normal cells. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving VSV-hIFNbeta-NIS with ruxolitinib phosphate may work better in treating patients with endometrial cancer compared to VSV-hIFNbeta-NIS alone.

开始日期2017-09-15

申办/合作机构

Mayo Clinic

[+1]

100 项与 VSV-IFNbeta-NIS 相关的临床结果

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100 项与 VSV-IFNbeta-NIS 相关的转化医学

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100 项与 VSV-IFNbeta-NIS 相关的专利（医药）

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项与 VSV-IFNbeta-NIS 相关的文献（医药）

2023-12-01·Molecular therapy oncolytics

Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma

Article

作者: Modiano, Jaime F ; Chehadeh, Andrea ; Henson, Michael S ; Cornax, Ingrid ; Suksanpaisan, Lukkana ; Makielski, Kelly M ; Borgatti, Antonella ; Tabaran, Alexandru-Flaviu ; Koopmeiners, Joseph S ; Pracht, Sara ; Stuebner, Kathleen M ; O'Sullivan, M Gerard ; Groschen, Donna ; Preusser, Caitlin ; Bergsrud, Kelly ; Winter, Amber ; Farrar, Michael A ; Sarver, Aaron L ; Cutter, Gary R ; Russell, Stephen J ; Schwabenlander, Marc D ; Wolfe, Melissa ; Mills, Lauren J ; Naik, Shruthi

Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we describe the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic vesicular stomatitis virus (VSV), VSV-IFNβ-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNβ-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a "tail" of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.

2023-01-01·Frontiers in immunology

Preclinical efficacy of oncolytic VSV-IFNβ in treating cancer: A systematic review.

Review

作者: Mahmoud, Ahmad Bakur ; Albaradie, Omar A ; Saeedi, Nizar H ; Alkayyal, Almohanad A ; Moglan, Abdulaziz Molham ; Samman, Yahya Marwan ; Alharbi, Hussam Mohsen ; Jalal, Mohammed M ; Alsayegh, Fares Fayez

Background:

Cancer incidence and mortality are increasing rapidly worldwide, necessitating further investigation into developing and optimizing emergent cancer therapies. Oncolytic viruses such as vesicular stomatitis virus encoding interferon β (VSV-IFNβ) have attracted considerable attention, as they offer great efficacy and safety profiles. This systematic review aimed to determine and compare the efficacy profile between VSV-IFNβ and non-treatment controls in preclinical cancer models.

Methodology:

The Embase and Medline databases were systematically searched for relevant studies using related key terms and Medical Subject Headings (MeSH). Titles, abstracts, and full texts were screened, and data from eligible articles were extracted by two groups independently and in duplicate (two reviewers per group). Disagreements were resolved by a fifth independent reviewer. The included articles were all preclinical (translational) in vivo English studies that investigated and compared the efficacy profile between VSV-IFNβ and non-treatment controls in animal models. The risk of bias among the studies was assessed by two reviewers independently and in duplicate using SYRCLE's risk-of-bias tool for animal studies; disparities were addressed by a third independent reviewer.

Results:

After employing relevant MeSH and key terms, we identified 1598 articles. A total of 87 articles were either duplicates or conference proceedings and were thus excluded. Following title and abstract screening, 37 articles were included in the full-text assessment. Finally, 14 studies met the eligibility criteria. Forty-two experiments from the included studies examined the potential efficacy of VSV-IFNβ through different routes of administration, including intratumoral, intraperitoneal, and intravenous routes. Thirty-seven experiments reported positive outcomes. Meanwhile, five experiments reported negative outcomes, three and two of which examined intratumoral and intravenous VSV-IFNβ administration, respectively.

Conclusion:

Although the majority of the included studies support the promising potential of VSV-IFNβ as an oncolytic virus, further research is necessary to ensure a safe and efficacious profile to translate its application into clinical trials.

Systematic review registration:

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022335418.

2020-08-01·Molecular cancer research : MCR2区 · 医学

Radiation Attenuates Prostate Tumor Antiviral Responses to Vesicular Stomatitis Virus Containing IFNβ, Resulting in Pronounced Antitumor Systemic Immune Responses

2区 · 医学

Article

作者: Barber, Glen ; Marples, Brian ; Udayakumar, Thirupandiyur S. ; Patel, Mausam ; Tao, Wensi ; Pollack, Alan ; Totiger, Tulasigeri M. ; Betancourt, Dillon M. ; Ahmad, Anis

Abstract:

Vesicular stomatitis virus (VSV) expressing IFNβ induces apoptosis in multiple tumor models while maintaining an excellent safety profile. VSV-IFNβ is oncoselective due to permissive replication in cells with an altered IFN pathway. The human VSV-IFNβ (hIFNβ) vector is currently used in clinical trials as a standalone therapy; however, we hypothesized that oncolytic virotherapy might be more effective when used in combination with radiotherapy (RT). We investigated the synergistic effects of RT and VSV-hIFNβ in the subcutaneous PC3 and orthotopic LNCaP prostate xenograft models and a syngeneic RM9 prostate tumor model. VSV-IFNβ combined with RT amplified tumor killing for PC3 and LNCaP xenografts, and RM9 tumors. This was attributed to the induction of proapoptotic genes leading to increased VSV-IFNβ infection and replication, VSV expression, and oncolysis. In the RM9 tumors, combination therapy resulted in a robust antitumor immune response. Treated RM9 tumor-bearing mice demonstrated an increase in CD8+ and CD4+ T-cell numbers, 100% resistance to tumor rechallenge, and reduced resistance to reimplantation challenge with CD8+ knockdown. RT enhanced the activity of VSV-mediated oncolysis via attenuation of the innate antiviral response, resulting in increased VSV replication and the generation of an adaptive immune response earmarked by an increase in CD8+ lymphocyte numbers and antitumor activity. Local tumor irradiation combined with VSV-IFNβ affects tumor cell death through direct and systemic activity in conjunction with pronounced antitumor immunity.

Implications::

Radiotherapy enhances VSV-mediated oncolysis and anti-tumor immunity, indicating that the ombination has promise for very high risk prostate cancer.

项与 VSV-IFNbeta-NIS 相关的新闻（医药）

2023-06-14

·PRNewswire

Vyriad Announces Expansion of T-Cell Lymphoma Trial at Mayo Clinic

More Patients Added to Phase 1 Trial Following Encouraging Early Results ROCHESTER, Minn., June 14, 2023 /PRNewswire/ -- Vyriad, Inc., announces an expansion of a Phase 1 investigator-initiated trial at Mayo Clinic evaluating the safety and efficacy of Voyager-V1 (VSV-hIFNbeta-NIS) in patients with peripheral T-cell lymphoma (PTCL) following encouraging initial results1. Voyager-V1 is an investigational therapy being co-developed with Regeneron Pharmaceuticals, Inc., to treat patients with recurrent or treatment resistant cancers. It is an oncolytic virotherapy designed to target and dissolve cancer cells and stimulate the patient's immune system in hopes of preventing recurrence. "The expansion of this Phase 1 program is an important step toward delivering targeted genetic medicines to patients with resistant PTCL," said Stephen J. Russell, MD, Ph.D., Vyriad's chief executive officer and chief scientific officer. "Early Phase 1 results offered an indication that a single infusion of Voyager-V1 has the potential to provide significant benefit to patients with PTCL, a cancer with a generally poor prognosis." PTCLs comprise a diverse group of uncommon and aggressive diseases in which the patient's T cells become cancerous. PTCLs are a varied group of diseases that are not well understood. Techniques to distinguish and study the various subtypes of PTCL have only recently been developed.2 Current first-line therapies for patients with PTCL can be curative, but most patients will experience a recurrence of the disease. Funding for the trial is provided by Regeneron, the National Institutes of Health, and Vyriad. The trial is being conducted at Mayo Clinic Rochester and Mayo Clinic Arizona. For more information on the Phase 1 study please visit Clinical Trials.Gov/study/NCT03017820. About Vyriad, Inc. Vyriad is a clinical-stage biotechnology company developing virus-based therapeutics, focusing initially on proprietary oncolytic virus therapies for the treatment of cancers with significant unmet needs. Our lead platforms, derived from either vesicular stomatitis virus (VSV) or measles virus, are being evaluated in ongoing Phase 1-2 clinical trials addressing multiple cancer types. Vyriad is a privately held company based in Rochester, Minnesota. For more information, visit . 1 5 of 9 patients experienced positive results in a trial published by Cook et al. Blood Advances. 2022. Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma. PMID: 35175355 2 Peripheral T-Cell Lymphoma Facts. Leukemia & Lymphoma Society. This communication contains information about an investigational product. This product is limited by Federal (U.S.) law to investigational use only. Vyriad makes no claims regarding the safety or effectiveness of the unapproved investigational product. The intent of providing this information is to convey research and development initiatives underway at Vyriad. Contact: Scott Beck Chief Operating Officer [email protected] SOURCE Vyriad, Inc.

临床1期临床结果

100 项与 VSV-IFNbeta-NIS 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
晚期头颈癌	临床2期	美国	Vyriad, Inc.初创企业	2020-04-24
晚期头颈癌	临床2期	巴西	Vyriad, Inc.初创企业	2020-04-24
结直肠癌	临床2期	美国	Vyriad, Inc.初创企业	2020-04-24
结直肠癌	临床2期	巴西	Vyriad, Inc.初创企业	2020-04-24
黑色素瘤	临床2期	美国	Vyriad, Inc.初创企业	2020-04-24
黑色素瘤	临床2期	巴西	Vyriad, Inc.初创企业	2020-04-24
头颈部鳞状细胞癌	临床2期	美国	Vyriad, Inc.初创企业	2020-04-24
头颈部鳞状细胞癌	临床2期	巴西	Vyriad, Inc.初创企业	2020-04-24
神经内分泌癌	临床2期	美国	Vyriad, Inc.初创企业	2019-04-09
非小细胞肺癌	临床2期	美国	Vyriad, Inc.初创企业	2019-04-09

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03017820 (ASCO2023) 人工标引	临床1期	血液肿瘤	30	Voyager-V1	膚遞鏇糧簾襯選網鏇範(衊蓋積醖簾壓襯選願膚) = 蓋鬱願壓製築築憲範夢艱顧膚鏇積膚夢獵艱遞 (鬱夢廠鹽襯觸積蓋製壓 ) 更多	积极	2023-05-31
NCT03017820 (ASCO2023) 人工标引	临床1期	复发性T细胞淋巴瘤	43	VSV-IFNbeta-NISS	糧衊廠壓繭繭築襯願鹽(鑰憲衊窪齋獵夢糧鹹鏇) = Grades 3 and higher AEs were hematologic with transient lymphopenia (63.6%), neutropenia (36.4%) being the most common. 鏇遞範鏇醖觸鬱選鹹顧 (餘構廠夢醖壓夢遞顧鑰 ) 更多	积极	2023-05-31
NCT03017820 (ASCO2021) 人工标引	临床1期	复发性T细胞淋巴瘤	15	VSV-IFNβ-NIS	鑰網積構襯鹽製範齋蓋(鏇願鏇鏇鏇遞憲淵簾蓋) = CRS grades 1 (6.7%) and 2 (46.6%) were the non-hematologic AEs of note. 願築顧遞壓選憲製糧廠 (鏇選壓壓糧醖選窪遞窪 ) 更多	积极	2021-05-20
NCT03120624 (Voyager-V1, ASGCT2019)	临床1期	转移性子宫内膜恶性肿瘤 \| 复发性子宫内膜癌 IFNβ levels \| RNAseq	7	VSV-IFNβ-NIS dose level 1	壓膚壓願願築繭餘窪醖(壓齋選構窪觸鏇繭壓獵) = N=2 鏇鬱簾壓觸鹹顧繭觸蓋 (繭艱膚範築網襯壓憲醖 ) 更多	积极	2019-04-22