Phase 1/2 Evaluation of Adenoviral p53 (Ad-p53) in Combination With Capecitabine (Xeloda) or Anti-PD-1 in Patients With Unresectable Liver Metastases of Colorectal Carcinoma(CRC) and Other Solid Tumors, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) and Primary Hepatic Cancers With Known Disease Progression on Standard Therapy

This is a Phase 1/2 study of the combination of Ad-p53 administered intra-arterially in combination with oral metronomic capecitabine or pembrolizumab in patients with unresectable, refractory liver metastases of colorectal carcinoma (CRC) and other solid tumors, including primary hepatocellular carcinoma (HCC). A third arm will study the intra-tumoral injection of Ad-p53 combined with nivolumab infusions in recurrent head and neck squamous cell cancer (HNSCC). This safety study has a standard 3+3 design for arms A and B; .HNSCC will be placed in a single dosing cohort. The Maximum Tolerated Dose (MTD) will be determined as well for intra-arterial infusions, and the entire study will determine the general efficacy using RECIST 1.1 and Immune-Related Response Criteria. Safety will be followed using the CTCAE listings for adverse events.

开始日期2018-11-20

申办/合作机构

Multivir, Inc.

NCT03544723 / Unknown status临床2期

A Phase 2, Multi-Center, Open Label Study to Evaluate Adenoviral p53 (Ad-p53) in Combination With Immune Checkpoint Inhibitor Therapy in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Tumors Approved for Anti-PD-1 or Anti-PD-L1 Therapy

This is a single arm Phase 2 study of the combination of adenoviral p53 (Ad-p53) gene therapy administered intra-tumorally with approved immune checkpoint inhibitors in patients with recurrent or metastatic cancers. Comparison will be made to historical data. General safety and efficacy using RECIST 1.1 and Immune-Related Response Criteria as well as ECOG performance will be utilized.

开始日期2018-10-01

申办/合作机构

Multivir, Inc.

NCT03406715 / Terminated临床2期IIT

Combination Immunotherapy With Ipilimumab and Nivolumab Plus a Dendritic Cell Based p53 Vaccine (Ad.p53-DC) in Patients With Relapsed Small Cell Lung Cancer (SCLC)

The purpose of this study is to find out what effects (good and bad) immunotherapy treatment using the p53 vaccine (Ad.p53-DC) in combination with Nivolumab and Ipilimumab has on small cell lung cancer. Immunotherapy is a cancer therapy that uses the body's immune system to fight cancer cells.
This study can be divided into three different phases: initial Induction Immunotherapy, Maintenance Immunotherapy and Retreatment.

开始日期2018-03-15

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+2]

100 项与 Multivir, Inc. 相关的临床结果

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0 项与 Multivir, Inc. 相关的专利（医药）

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项与 Multivir, Inc. 相关的文献（医药）

2022-06-01·Cancer gene therapy2区 · 医学

Tumor suppressor immune gene therapy to reverse immunotherapy resistance

2区 · 医学

Article

作者: Sellman, Beatha ; Chada, Sunil ; Wiederhold, Dora ; Menander, Kerstin B ; Ahn, Hyo Min ; Jung, Bo-Kyeong ; Talbott, Max ; Sobol, Robert E ; Nemunaitis, John J ; Yun, Chae-Ok

Abstract:

Background:

While immune checkpoint inhibitors are becoming a standard of care for multiple types of cancer, the majority of patients do not respond to this form of immunotherapy. New approaches are required to overcome resistance to immunotherapies.

Methods:

We investigated the effects of adenoviral p53 (Ad-p53) gene therapy in combination with immune checkpoint inhibitors and selective IL2 or IL15 CD122/132 agonists in the aggressive B16F10 tumor model resistant to immunotherapies. To assess potential mechanisms of action, pre- and post- Ad-p53 treatment biopsies were evaluated for changes in gene-expression profiles by Nanostring IO 360 assays.

Results:

The substantial synergy of “triplet” Ad-p53 + CD122/132 + anti-PD-1 therapy resulted in potential curative effects associated with the complete tumor remissions of both the primary and contralateral tumors. Interestingly, contralateral tumors, which were not injected with Ad-p53 showed robust abscopal effects resulting in statistically significant decreases in tumor size and increased survival (p < 0.001). None of the monotherapies or doublet treatments induced the complete tumor regressions. Ad-p53 treatment increased interferon, CD8+ T cell, immuno-proteosome antigen presentation, and tumor inflammation gene signatures. Ad-p53 treatment also decreased immune-suppressive TGF-beta, beta-catenin, macrophage, and endothelium gene signatures, which may contribute to enhanced immune checkpoint inhibitor (CPI) efficacy. Unexpectedly, a number of previously unidentified, strongly p53 downregulated genes associated with stromal pathways and IL10 expression identified novel anticancer therapeutic applications.

Conclusions:

These results imply the ability of Ad-p53 to induce efficacious local and systemic antitumor immune responses with the potential to reverse resistance to immune checkpoint inhibitor therapy when combined with CD122/132 agonists and immune checkpoint blockade. Our findings further imply that Ad-p53 has multiple complementary immune mechanisms of action, which support future clinical evaluation of triplet Ad-p53, CD122/132 agonist, and immune checkpoint inhibitor combination treatment.

Frontiers in Oncology3区 · 医学

Analysis of Adenoviral p53 Gene Therapy Clinical Trials in Recurrent Head and Neck Squamous Cell Carcinoma

3区 · 医学

ArticleOA

作者: Sellman, Beatha ; Menander, Kerstin B ; Talbott, Max ; Sobol, Robert E ; Chada, Sunil ; Nemunaitis, John J ; Wiederhold, Dora

Background:

We conducted an analysis of previous adenoviral p53 (Ad-p53) treatment data in recurrent head and neck squamous cell carcinoma (HNSCC) patients to identify optimal Ad-p53 treatment methods for future clinical trials.

Methods:

The analysis involved recurrent HNSCC patients treated with Ad-p53 for whom p53 genotyping and immunohistochemistry tumor biomarker studies had been performed (n = 70). Ad-p53 tumor treatment responses defined by RECIST 1.1 criteria were correlated with Ad-p53 dose and tumor p53 biomarkers. Gene expression profiles induced by Ad-p53 treatment were evaluated using the Nanostring IO 360 panel.

Results:

Ad-p53 dose based upon the injected tumor volume had a critical effect on tumor responses. All responders had received Ad-p53 doses greater than 7 × 1010 viral particles/cm3 of tumor volume. There was a statistically significant difference in tumor responses between patients treated with greater than 7 × 1010 viral particles/cm3 compared to patients treated at lower Ad-p53 doses (Tumor Response 31% (9/29) for Ad-p53 > 7 × 1010 viral particles/cm3 versus 0% (0/25) for Ad-p53 < 7 × 1010 viral particles/cm3; p = 0.0023). All responders were found to have favorable p53 biomarker profiles defined by less than 20% p53 positive tumor cells by immunohistochemistry (IHC), wild type p53 gene sequence or p53 deletions, truncations, or frame-shift mutations without functional p53 tetramerization domains. Preliminary gene expression profiling results revealed that Ad-p53 treatment increased interferon signaling, decreased TGF-beta and beta-catenin signaling resulting in an increased CD8+ T cell signature which are associated with increased responses to immune checkpoint blockade.

Conclusions:

Our findings have important implications for future p53 targeted cancer treatments and identify fundamental principles to guide Ad-p53 gene therapy. We discovered that previous Ad-p53 clinical trials were negatively impacted by the inclusion of patients with unfavorable p53 biomarker profiles and by under dosing of Ad-p53 treatment. Future Ad-p53 clinical trials should have favorable p53 biomarker profiles inclusion criteria and Ad-p53 dosing above 7 × 1010 viral particles/cm3 of injected tumor volume. Preliminary gene expression profiling identified p53 mechanisms of action associated with responses to immune checkpoint blockade supporting evaluation of Ad-p53 in combination with immune checkpoint inhibitors.

项与 Multivir, Inc. 相关的新闻（医药）

2021-02-15

·GlobeNewswire

Global Gene Therapy Market Outlook to 2030 - by Therapeutic Approach, Type of Gene Therapy, Type of Vectors Used, Therapeutic Areas, Route of Administration and Key Geographical Regions

Dublin, Feb. 15, 2021 (GLOBE NEWSWIRE) -- The "Gene Therapy Market by Therapeutic Approach, Type of Gene Therapy, Type of Vectors Used, Therapeutic Areas, Route of Administration, and Key Geographical Regions: Industry Trends and Global Forecasts, 2020-2030" report has been added to ResearchAndMarkets.com's offering. Over time, several gene therapies have been developed for the treatment of both simple and complex genetic disorders. In fact, there are 10 approved gene therapies (recent examples include Zolgensma, ZyntegloT and Collategene) to date, and more than a thousand product candidates being evaluated in clinical trials, worldwide. Considering the current pace of research and product development activity in this field, experts believe that the number of clinical research initiatives involving gene therapies are likely to grow by 17% annually. In this context, the USFDA released a notification, mentioning that it now expects to receive twice as many gene therapy applications each year, starting 2020. Despite the ongoing pandemic, it is worth highlighting that gene therapy companies raised approximately USD 5.5 billion in capital investments, in 2020 alone. This is indicative of the promising therapeutic potential of this emerging class of pharmacological interventions, which has led investors to bet heavily on the success of different gene therapy candidates in the long term. Several technology platforms are currently available for discovery and development of various types of gene therapies. In fact, advances in bioanalytical methods and genome editing and manipulation technologies, have enabled the development of novel therapy development tools/platforms. In fact, technology licensing is a lucrative source of income for stakeholders in this industry, particularly for those with proprietary gene editing platforms. Given the growing demand for interventions that focus on the amelioration of the underlying (genetic) causes of diseases, it is expected that the gene therapy pipeline will continue to steadily expand. Moreover, promising results from ongoing clinical research initiatives are likely to bring in more investments to support therapy product development initiatives in this domain. Therefore, we are led to believe that the global gene therapy market is poised to witness significant growth in the foreseen future. The report features an extensive study of the current market landscape of gene therapies, primarily focusing on gene augmentation-based therapies, oncolytic viral therapies, immunotherapies and gene editing therapies. The study also features an elaborate discussion on the future potential of this evolving market. Key Questions Answered Who are the leading industry players engaged in the development of gene therapies? How many gene therapy candidates are present in the current development pipeline? Which key disease indications are targeted by such products? Which types of vectors are most commonly used for effective delivery of gene therapies? What are the key regulatory requirements for gene therapy approval, across various geographies? Which commercialization strategies are most commonly adopted by gene therapy developers, across different stages of development? What are the different pricing models and reimbursement strategies currently being adopted for gene therapies? What are the various technology platforms that are either available in the market or are being designed for the development of gene therapies? Who are the key CMOs/CDMOs engaged in supplying viral/plasmid vectors for gene therapy development? What are the key value drivers of the merger and acquisition activity in the gene therapy industry? Who are the key stakeholders that have actively made investments in the gene therapy domain? Which are the most active trial sites related to this domain? How is the current and future market opportunity likely to be distributed across key market segments? Key Topics Covered: 1. PREFACE 2. EXECUTIVE SUMMARY 3. INTRODUCTION 4. GENE DELIVERY VECTORS 5. REGULATORY LANDSCAPE AND REIMBURSEMENT SCENARIO 6. MARKET OVERVIEW 7. COMPETITIVE LANDSCAPE 8. MARKETED GENE THERAPIES 9. KEY COMMERCIALIZATION STRATEGIES 10. LATE STAGE GENE THERAPIES 11. EMERGING TECHNOLOGIES 12. KEY THERAPEUTICS AREAS 13. PATENT ANALYSIS 14. MERGERS AND ACQUISITIONS 15. FUNDING AND INVESTMENT ANALYSIS 16. CLINICAL TRIAL ANALYSIS 17. COST PRICE ANALYSIS 18. BIG PHARMA PLAYERS: ANALYSIS OF GENE THERAPY RELATED INITIATIVES 19. DEMAND ANALYSIS 20. MARKET FORECAST AND OPPORTUNITY ANALYSIS 21. VECTOR MANUFACTURING 22. CASE STUDY: GENE THERAPY SUPPLY CHAIN 23. CONCLUSION A Selection of Companies Mentioned Include: 4BIO Capital 4D Molecular Therapeutics AavantiBio aaVective AAVogen AbbVie Allergan AlphaVax Altheia Science Amgen Amplo Angionetics ApolloBio Arthrogen Astellas Pharma AstraZeneca Atlas Venture Atsena Therapeutics AVROBIO Baillie Gifford Baldota Group Bayer Biogen BridgeBio Bristol-Myers Squibb Calimmune Cardiogen Sciences Casdin Capital Codexis CSL Behring Editas Medicine Fundacion Sanfilippo B Google Ventures Gradalis Green Cross Holdings GSK Handl Therapeutics Hovione Scientia Intrexon Invus IVERIC bio Janssen Pharmaceuticals Johnson & Johnson Development Juda Capital K2 Venture Capital Lacerta Therapeutics MeiraGTx Merck MERITZ Securities Mitsubishi Tanabe Pharma MultiVir Myonexus Therapeutics Navega Therapeutics NeoMed Nerveda Omega Funds Omnes Capital OrbiMed ORI Capital Otonomy Oxford BioMedica Oxular REGENXBIO Renova Therapeutics Roche Sanofi StrideBio Surveyor Capital Syncona Synpromics T. Rowe Price Takeda Pharmaceutical Targovax Temasek Tenaya Therapeutics TheraBiologics Theravectys Tocagen WuXi AppTec XyloCor Therapeutics Ysios Capital Ziopharm Oncology For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. CONTACT: ResearchAndMarkets.com Laura Wood, Senior Press Manager press@researchandmarkets.com For E.S.T Office Hours Call 1-917-300-0470 For U.S./CAN Toll Free Call 1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

基因疗法并购

2021-02-15

·佰傲谷BioValley

Moderna，CureVac，BioNTech和GSK共拥近50%的专利申请—mRNA疫苗知识产权格局

▲速抢免费参会名额 | 大湾区(广州)生物医药创新者峰会 mRNA疫苗有望取代传统疫苗平台，因为mRNA疫苗可以快速生产并针对各种条件进行定制。在临床研究中，针对各种传染病和癌症的mRNA疫苗通常是安全且耐受性良好的。在过去的几年中，已经在免疫原性和功效研究中改进和验证了多种mRNA疫苗。目前正在预防COVID-19（由SARS-CoV-2引起）的临床试验中的四种候选疫苗是mRNA疫苗：mRNA-1273（Moderna），BNT-162（BioNTech），CVnCoV（CureVac）和LNP -nCoVsaRNA（伦敦帝国学院）。为了更好地了解围绕mRNA疫苗开发的知识产权（IP），研究者通过审查和索引2010年1月至4月间发布的美国，欧洲和国际英语（专利合作条约涵盖）专利和申请的索引，从而形成了详细的IP格局。2020年（补充信息）。文件仅限于包含声称限于mRNA编码疫苗的文件。研究者确定了113个与搜索焦点相关的INPADOC专利家族，这些专利家族通过基于权利要求的适应症，递送方法和药理修饰进行索引（图1）。图1 | 基于适应症重点和优化方法的mRNA疫苗专利申请活动 a.| 根据归档年份和适应症重点(传染病、癌症和平台) 绘制。b | 通过提交年份和优化方法来绘制专利文件，以解决mRNA的不稳定性，体内递送效率低下和固有免疫原性问题。圆圈根据优化方法进行了着色，圆圈的区域表示特定年份提交的专利或申请的总数。同心圆上的区域表示给定年份中要求通过脂质纳米颗粒交付的专利或申请的数量。在过去的五年中，针对传染病和癌症的专利申请活动急剧增长。在过去的三年中，传染病适应症的申请数量超过了癌症的适应症，这可能反映出在MERS-CoV，埃博拉病毒和Zika病毒流行后，人们对疫苗的兴趣日益增加。2019年8月，Moderna因正在研究的Zika病毒疫苗（mRNA-1893）获得了FDA快速通道指定，目前正在I期研究中进行评估。从收集到的文件中产生了声称mRNA疫苗的受让人的专利趋势。大约70％的专利家族是由行业提交的（113个专利中有80个）。在总共56名受让人中，近一半（26）是公司，其中超过三分之一（10; 38％）是公开交易的。其余54％（30）的受让人是研究机构或独立发明家。该领域高度分散，包括拜耳，勃林格殷格翰，百时美施贵宝，葛兰素史克（GSK）和久光制药等跨国公司。葛兰素史克（GSK）目前正在I期临床试验中使用内置佐剂测试自我扩增mRNA疫苗以治疗狂犬病。较小的公司，例如Morphogenesis，Multivir，Nantbio和Translate Bio（以前称为RaNA Therapeutics），各自在针对癌症治疗的mRNA疫苗方面拥有较小的IP产品组合。 Moderna，CureVac，BioNTech和GSK共同拥有mRNA疫苗专利申请的近一半。 Moderna于2020年7月开始对其SARS-CoV-2 mRNA疫苗进行III期临床试验，并提供了9种预防性疫苗（包括巨细胞病毒和Zika病毒）的I期阳性数据。 BioNTech与辉瑞公司合作，正在I / II期临床试验中检测四种针对SARS-CoV-2的疫苗，并于7月启动了其中一种BNT162b2的II / III期临床试验。 CureVac于2020年6月用其领先的SARS-CoV-2 mRNA疫苗候选药物启动了I / IIa期临床试验，伦敦帝国学院也启动了I期临床试验，于2020年6月进行了自我扩增RNA疫苗的研发。总结总体申请活动表明，越来越多的专利保护法以改善由载体即脂质纳米颗粒（LNP）组合载体递送的mRNA的mRNA递送效率。许多专利保护药理学修饰以减少mRNA的不稳定性和先天免疫原性（图1b）。研究者预计，随着对mRNA疫苗平台投资的增加以及正在进行的、加速的临床试验，该领域将呈指数增长，这些试验可能是mRNA疫苗概念的证明。这些试验中的积极结果不仅可以解决对SARS-CoV-2疫苗的紧迫需求，而且还为将来的传染病暴发提供了有效而多功能的治疗工具。参考文献 1. https://www.nature.com/articles/d41573-020-00119-8 版权声明：本文转自佰傲谷BioValley，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看

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药物(靶点)	适应症	全球最高研发状态

Oncolytic adenovirus gene therapy(Multivir, Inc.) ( ADP )	肿瘤更多	临床1期
Interleukin 24 gene therapy(Multivir, Inc.) ( IL-24 )	头颈部肿瘤更多	无进展
HSV-Rb-p450	结直肠癌更多	无进展
HSV Rb-p450 gene therapy(Multivir, Inc.) ( CYPs )	结直肠癌更多	无进展