The clinical data includes details of immunologic trends in patients with recurrent high-grade glioma (rHGG) from a Phase 1 study of Toca 511 (vocimagene amiretrorepvec) and Toca FC (flucytosine, extended-release). Additionally, new preclinical data will be presented demonstrating increased survival from the combination of Toca 511 and flucytosine with either temozolomide or cyclophosphamide.
Summaries are provided below; full posters or presentations will be placed on Tocagen's website following the presentation.
Details of the AACR presentation are as follows:
Presentation Type: Poster (Abstract: 4771)
Title: The addition of Toca 511 and 5-FC to temozolomide improves response in a temozolomide-resistant murine glioblastoma model and correlates with Toca 511 dose
Presenter: Maria E. Rodriguez-Aguirre
Date and Time: Wednesday, April 3, 8:00 a.m.-12:00 p.m. ET
- This study aimed to assess the interaction of temozolomide with escalating doses of Toca 511 in an orthotopic temozolomide-resistant murine glioma model.
- Even with lympho-depleting temozolomide treatment, survival was prolonged with moderate levels (30-50 percent) of tumor transduction of Toca 511 with 5-FC but not with lower transduction rates (10 percent).
- Data from this study may inform the evaluation of Toca 511 & Toca FC in combination with temozolomide in patients with newly diagnosed glioblastoma (GBM).
Details of the AANS presentations are as follows:
Presentation Type: E-Poster displayed online (Abstract: 2120)
Title: Immune Monitoring of High-Grade Glioma Patients in a Phase 1 Clinical Trial of Toca 511 and Toca FC
Presenter: Steven Kalkanis, M.D.
- Human immune monitoring results from a Phase 1 clinical trial of Toca 511 & Toca FC support an immune-related mechanism of action for the regimen.
- Univariate comparisons and multivariate models revealed pre-treatment tumor infiltrating cell subsets quantified via deconvolution of RNA sequencing data were associated with both objective responses and survival.
- Post-treatment serum cytokine time-course results suggest that differences in temporal modulations are associated with both objective response and survival.
- These results indicate the value of evaluating potential biomarkers of patient outcomes in the ongoing randomized Toca 5 Phase 3 trial in patients with recurrent HGG.
Presentation Type: Oral (Abstract: 481)
Title: Toca 511 and 5-FC in Combination with Metronomic Cyclophosphamide Reduces Treg Cells and Enhances Therapy Efficacy in a Preclinical Murine Model
Presenter: David Piccioni, M.D., Ph.D.
Date and Time: Wednesday, April 17, 4:49-4:52 p.m. PT
- This study aimed to determine if the addition of metronomic cyclophosphamide would provide therapeutic benefit when combined with Toca 511 and 5-FC (5-fluorocytosine) in a preclinical, subcutaneous glioma model.
- The addition of metronomic cyclophosphamide improved tumor control and survival, and led to a superior CD8+/Treg ratio in the peripheral blood.
- Results support the further evaluation of Toca 511 & Toca FC with metronomic dosing of cyclophosphamide and potentially other chemotherapeutics.
About Toca 511 & Toca FC
Tocagen's lead product candidate is a two-part cancer-selective immunotherapy comprising an investigational biologic, Toca 511 (vocimagene amiretrorepvec), and an investigational small molecule, Toca FC (flucytosine, extended-release). Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells resulting in anti-cancer immune activation and subsequent tumor killing.
Tocagen is a clinical-stage, cancer-selective gene therapy company developing first-in-class, broadly applicable product candidates designed to activate a patient's immune system against their own cancer. Tocagen's lead investigational product candidate, Toca 511 & Toca FC, is under evaluation in a pivotal Phase 3 trial (Toca 5) for recurrent high grade glioma (HGG), a disease with significant unmet medical need. The U.S. Food and Drug Administration awarded Tocagen an orphan drug grant for the Toca 5 trial and has granted Toca 511 & Toca FC Breakthrough Therapy Designation for the treatment of recurrent HGG. The European Medicines Agency has granted Toca 511 PRIME (PRIority MEdicines) designation for the treatment of glioma.
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