INTRAVESICAL ONCOLYTIC THERAPY FOR BLADDER CANCER

膀胱癌膀胱内溶瘤治疗

• 批准号: 9407690
• 负责人: Rosa Maria Diaz
• 金额: $ 15.68万
• 依托单位: VYRIAD, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9407690
• 关键词: Antibodies; BCG Vaccine; Bladder; Bladder Neoplasm; Bladder Tissue; Blood; Cancer Etiology; Cancer Patient; Cancer cell line; Caring; Cause of Death; Cessation of life; Clinic; Clinical; Clinical Trials; Clinical Trials Design; Cystectomy; Cytolysis; Data; Development; Diagnosis; Disease; Disease Progression; Dose; Engineering; Evaluation; Excision; FDA approved; Future; Goals; Grant; Head and Neck Cancer; Hospitals; Immune; Immune checkpoint inhibitor; Immune response; Immunotherapy; In Vitro; In complete remission; Infection; Inflammatory; Intravenous; Intravesical Administration; Investigation; Lead; Letters; Malignant Epithelial Cell; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of urinary bladder; Measles; Measles virus; Measurable; Mediating; Mesothelioma; Monitor; Multiple Myeloma; Muscle; Mutation; Neoadjuvant Therapy; Neoplasm Metastasis; Oncolytic; Oncolytic viruses; Pathologic; Patient Schedules; Patients; Phase I Clinical Trials; Predisposition; Protocols documentation; Quality of life; Radical Cystectomy; Recruitment Activity; Regimen; Research Design; Route; Safety; Small Business Innovation Research Grant; Specimen; T cell response; T-Lymphocyte; Testing; Therapeutic; Time; Transitional Cell Carcinoma; Transurethral Resection; Treatment Efficacy; Tumor Antigens; Tumor Immunity; Urine; Urologist; Urology; Viral; Viremia; Virus; Virus Replication; anticancer activity; cancer cell; cancer immunotherapy; cancer therapy; chemotherapy; cost; design; effective therapy; efficacy study; immune activation; improved; innovation; insight; intraperitoneal; intravesical; killings; neoplastic cell; new product development; novel; novel therapeutic intervention; oncolysis; oncolytic virotherapy; response; safety and feasibility; standard of care; treatment response; tumor

PROJECT SUMMARY/ABSTRACT . Bladder cancer is a leading cause of death in the US and the most expensive cancer to treat. Despite this, there has been only one new bladder cancer therapy, the checkpoint inhibitor atezoluzimab, approved in the past 30 years. Oncolytic viruses, viruses that selectively infect and kill cancer cells, are a potent new class of immunotherapy that mediate anticancer activity by direct virus induced killing and robust activation of immune responses against tumor associated antigens. Vyriad's lead oncolytic measles virus product, MV-NIS, has shown clinical safety and efficacy following intravenous and intraperitoneal treatment in patients with advanced multiple myeloma and ovarian cancer respectively and potently kills bladder cancer cell lines in in vitro studies. Our goal is to develop oncolytic MV-NIS as a new treatment for bladder cancer, a malignancy that has demonstrated susceptibility to immunotherapy. A majority of patients are diagnosed with non-muscle invasive disease (NMIBC), of which approximately 50% of patients fail first line therapy. These patients, and patients with muscle invasive disease (MIBC), have no effective therapeutic options and facing the likelihood of disease progression or metastasis,often undergo radical cystectomy (complete bladder removal) which significantly impacts quality of life. In this SBIR fast-track application we propose to (I) confirm feasibility and identify optimal conditions for intravesical administration of MV-NIS and (II) carry out a Phase 1 clinical trial to evaluate intravesical MV-NIS therapy in patients scheduled to undergo radical cystectomy. This study will provide the critical demonstration of feasibility and safety of intravesical MV-NIS administration, as well preliminary indication of therapeutic efficacy to inform the decision to advance MV-NIS therapy in a pivotal clinical trial to seek approval as a novel bladder cancer therapy. We utilize an innovative clinical trial design that allows correlative analysis to define mechanism of action of MV-NIS therapy including characterization of antitumor immune responses. This will inform future studies to combine MV-NIS therapy with approved checkpoint inhibitors to potentially develop a more potent therapeutic approach for patients with locally advanced or metastatic bladder cancer. We are bringing together Vyriad's team, leading experts in oncolytic virotherapy development, with Mayo Clinic's nationally number one ranked Urology department, to perform this study that will, if successful, lead to the approval of a new, much-needed treatment for bladder cancer patients.

项目摘要/摘要。