INTRAVESICAL ONCOLYTIC THERAPY FOR BLADDER CANCER

PROJECT SUMMARY ABSTRACTBladder cancer is a leading cause of death in the US and the most expensive cancer to treatDespite thisthere has been only one new bladder cancer therapythe checkpoint inhibitor atezoluzimabapproved in the pastyearsOncolytic virusesviruses that selectively infect and kill cancer cellsare a potent new class of immunotherapy that mediate anticancer activity by direct virus induced killing and robust activation of immune responses against tumor associated antigensVyriadandapos s lead oncolytic measles virus productMV NIShas 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 studiesOur goal is to develop oncolytic MV NIS as a new treatment for bladder cancera malignancy that has demonstrated susceptibility to immunotherapyA majority of patients are diagnosed with non muscle invasive diseaseNMIBCof which approximatelyof patients fail first line therapyThese patientsand patients with muscle invasive diseaseMIBChave no effective therapeutic options and facing the likelihood of disease progression or metastasis often undergo radical cystectomycomplete bladder removalwhich significantly impacts quality of lifeIn this SBIR fast track application we propose toIconfirm feasibility and identify optimal conditions for intravesical administration of MV NIS andIIcarry out a Phaseclinical trial to evaluate intravesical MV NIS therapy in patients scheduled to undergo radical cystectomyThis study will provide the critical demonstration of feasibility and safety of intravesical MV NIS administrationas 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 therapyWe utilize an innovative clinical trial design that allows correlative analysis to define mechanism of action of MV NIS therapy including characterization of antitumor immune responsesThis 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 cancerWe are bringing together Vyriadandapos s teamleading experts in oncolytic virotherapy developmentwith Mayo Clinicandapos s nationally number one ranked Urology departmentto perform this study that willif successfullead to the approval of a newmuch needed treatment for bladder cancer patients PROJECT NARRATIVEBladder cancer is a leading cause of death in the US associated with a poor quality of lifehigh cost of care and few effective treatment optionsOncolytic virotherapy is a powerful new therapeutic approach utilizing engineered viruses to destroy cancerOur goal is develop Vyriadandapos s lead oncolytic measles productMV NISas potent and safe intravesical therapy to improve treatment and quality of life for bladder cancer patients