A Phase I Dose escalation Study of Intraperitoneal CYN as Consolidation Immunotherapy in Women with Residual or Recurrent Ovarian Cancer Status after Chemotherapy

DESCRIPTION provided by applicant A description of the problem In many cases of advanced epithelial ovarian cancer EOC the standard treatment of cytoreductive surgery is not technically possible and though of ovarian cancer patients initially respond to platinum based chemotherapy the majority experience recurrence and of patients die within years New therapeutic approaches are urgently needed Description of the product technology Cynvec and NYUMC are developing novel oncolytic immunotherapeutic Sindbis viral vectors SV which have a number of important advantages SV vectors have been shown to specifically target tumors by interaction with the high affinity laminin receptor LAMR which is over expressed by many tumors without infecting normal tissues Because SV is a blood borne virus with a relatively long half life it reaches distant cells including disseminated metastatic tumor cells In animal studies SV vectors are capable of achieving complete remissions and prevention of tumor recurrences The technical Innovation of the product To our knowledge there is no viral vector currently in use that can target tumors with the selectivity of SV Additionally SV vectors can induce an effective diversified anti tumor T cell response that eliminates tumor escape variants seen with more conventional therapies Hypothesis SV vectors represent a novel platform technology with potentially broad applicability to many types of metastatic cancer and in particular EOC Specific Aims Cynvecandapos s goal is to initiate clinical trials in women with EOC which have received chemotherapy platinum pretreatment within months of receiving an SBIR award Equivalent Phase I studies have been performed demonstrating feasibility including animal efficacy toxicology pharmacology and dose ranging studies SV vectors have been produced under GMP conditions at titers in excess of viral units ml A Pre IND meeting with the FDA has taken place and only limited studies were suggested prior to submission of an Investigational New Drug Application IND Cynvec aims to Complete FDA mandated preclinical studies so that an IND can be filed Success Criterion file an IND Demonstrate safety in Phase I human trials Success criterion determination of maximum tolerated dosage that has the potential to be efficacious Demonstrate appropriate immunological response in humans Success criterion observe NK and T cell responses similar to those associated with efficacy in mouse studies Commercial Opportunity Approximately $ billion is spent in the U S each year treating ovarian cancer The size of the market the likelihood that most patients will become resistant to current therapies and the increased use of combination therapies suggests that there is a significant opportunity for a new therapeutic Cynvecandapos s strategy for moving forward is partnering which first requires further validation with human studies PUBLIC HEALTH RELEVANCE In spite of significant progress in cancer therapies mortality rates for most malignancies remain high The classical regimen of cancer therapy e g chemotherapy and radiotherapy has a narrow therapeutic index that is further reduced by drug resistance that develops among tumor cells and is often associated with severe side effects Therefore we propose a viral immunotherapy clinical trial using novel and safer vectors that have the potential to cure tumor metastasis and prevent relapse