Toca 5 Phase 3 Trial Results Presented at the Society for Neuro-Oncology Annual Meeting

SAN DIEGO, Nov. 22, 2019

Trial design and demographics
Toca 5 was a Phase 3 randomized trial of Toca 511 & Toca FC in patients with recurrent HGG, undergoing resection. The trial involved 67 sites globally and enrolled 403 patients. Patients were randomized 1:1 prior to surgical resection to receive either the Toca 511 & Toca FC regimen or standard of care (SOC) treatment (lomustine, temozolomide or bevacizumab). The primary endpoint of the trial was overall survival (OS) and secondary endpoints included durable response rate, durable clinical benefit rate, duration of durable response and overall survival at 12 months. Patients were stratified based on IDH1 mutation status, KPS and geographic region. The baseline demographics and disease characteristics of the study were well balanced in the intent to treat populations and the 26 pre-specified subgroups.

Results
As previously announced, the trial did not meet the primary or secondary endpoints. The safety, tolerability and adverse event profile of Toca 511 & Toca FC was as expected for this patient population. In the ITT population, the median number of cycles of Toca FC was two and the median number of cycles across the SOC options ranged from two to four.

In a pre-planned subgroup analysis, subjects with second recurrence (N=60) showed a 57% risk reduction for death when treated with Toca 511 and Toca FC (21.82 months median OS compared to 11.14 months, HR=0.43, p=0.0162) representing an approximate doubling of survival. Further analysis of the second recurrence subgroup showed that patients with IDH1 mutations and anaplastic astrocytoma (AA), had the greatest survival benefit (HR=0.102, p=0.009). Second recurrence patients with IDH1 mutations and AA received a median of six cycles of Toca FC compared to a median of three cycles across the SOC options.

"The positive outcome for patients at second recurrence in the Toca 5 trial are compelling, despite the disappointment of the overall trial results," said Dr. Cloughesy. "Combined with an acceptable safety profile, these data support a potential opportunity to address the high unmet needs of this well-defined patient population and should inform any future development of the Toca 511 & Toca FC regimen."

In addition, molecular data from the Toca 5 trial were presented by Michael A. Vogelbaum, M.D., Ph.D., program leader of neuro-oncology and chief of neurosurgery at the Moffitt Cancer Center, at the Society for Neuro-Oncology and Society for CNS Interstitial Delivery of Therapeutics' 3rd Joint Conference on Therapeutic Delivery to the CNS. Data indicated that the immunological profile at baseline was well balanced between the two arms of the trial. In addition, data showed that patients in the second recurrence, IDH1 mutations and AA subgroups had a more robust immune profile prior to treatment. These data suggest that patients within these subgroups may have been favorably predisposed to generate anti-tumor immune responses.