A Phase I/IIa Study to Evaluate the Efficacy of Toca 511/Toca FC with Standard of Care Therapy in Newly Diagnosed High Grade Glioma
Grant Award Details
Grant Type:
Grant Number:
CLIN2-15311
Investigator(s):
Award Value:
$11,807,220
Status:
Pre-Active
Grant Application Details
Application Title:
A Phase I/IIa Study to Evaluate the Efficacy of Toca 511/Toca FC with Standard of Care Therapy in Newly Diagnosed High Grade Glioma
Public Abstract:
Therapeutic Candidate or Device
DB107 (Toca 511), a retroviral replicating vector expressing yeast cytosine deaminase, which converts an antifungal prodrug to an anticancer drug
Indication
Newly diagnosed high-grade glioma
Therapeutic Mechanism
Retroviral replicating vector DB107 (Toca 511) spreads through tumors and delivers yeast cytosine deaminase (CD), which converts the antifungal prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU) within infected cancer cells, resulting in direct cell killing and radiosensitization. In addition, 'bystander' effects of intratumorally generated 5-FU also eliminate immunosuppressive myeloid cells in the tumor microenvironment, enabling activation of anti-tumor immunity.
Unmet Medical Need
Malignant gliomas account for 70% of primary brain tumors. Standard of care consisting of resection, radiation and temozolomide results in a PFS of 6.9 months and overall survival of 14.6 months. Overall prognosis for this disease remains poor and remains a critical unmet need.
Project Objective
Completion of Phase 1/2a trial
Major Proposed Activities
DB107 (Toca 511), a retroviral replicating vector expressing yeast cytosine deaminase, which converts an antifungal prodrug to an anticancer drug
Indication
Newly diagnosed high-grade glioma
Therapeutic Mechanism
Retroviral replicating vector DB107 (Toca 511) spreads through tumors and delivers yeast cytosine deaminase (CD), which converts the antifungal prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU) within infected cancer cells, resulting in direct cell killing and radiosensitization. In addition, 'bystander' effects of intratumorally generated 5-FU also eliminate immunosuppressive myeloid cells in the tumor microenvironment, enabling activation of anti-tumor immunity.
Unmet Medical Need
Malignant gliomas account for 70% of primary brain tumors. Standard of care consisting of resection, radiation and temozolomide results in a PFS of 6.9 months and overall survival of 14.6 months. Overall prognosis for this disease remains poor and remains a critical unmet need.
Project Objective
Completion of Phase 1/2a trial
Major Proposed Activities
- Clinical trial initiation and implementation
- Correlative research studies
Statement of Benefit to California:
This first-in-human clinical trial will evaluate the safety and efficacy of a novel gene therapy technology in newly diagnosed high-grade glioma patients. This trial will be conducted at 3 institutions in California (UCSF, USC, UCSD). The Investigational Product was spun out of UCLA and USC, and a candidate biomarker has been identified by a California based company.