ATIM-05. COMPLEMENTARY CLINICAL AND ANCILLARY DATA FROM 123 PATIENTS WITH RECURRENT HIGH GRADE GLIOMA FROM THREE PHASE 1 TRIALS OF TOCA 511 AND TOCA FC: UPDATE AND JUSTIFICATION FOR A PHASE 2/3 TRIAL
Bibliographic record
Abstract
Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector. The vector infects human cells with selectivity for cancer cells because genome integration is dependent on cell division and viral replication is inhibited by innate and adaptive immune responses, defective in malignant tissues. Toca 511 spreads through cancer cells and stably delivers the gene for an optimized yeast cytosine deaminase that converts courses of the prodrug Toca FC (an investigational, extended-release version of 5-fluorocytosine) into 5-fluorouracil (5-FU). The 5-FU directly kills cancer cells likely leading to activation of antigen presenting cells in the tumor microenvironment. 5-FU can also diffuse into nearby immunosuppressive myeloid cells and kill them, leading to further activation of the immune system against the tumor by removing an important inflammatory brake. The safety, viral kinetics, immune response, and preliminary efficacy of Toca 511 and Toca FC have been investigated since 2010 in three, open-label, ascending dose, Phase 1 studies of 123 patients with recurrent high grade glioma (rHGG), each evaluating different methods of Toca 511 administration (intratumoral injection, injection into the cavity wall following resection, and intravenous injection followed by resection and injection into resection cavity wall) followed by multiple courses of oral Toca FC. Results to date include good tolerability; no persistent viremia; successful gene transduction within resected tumors; and median overall survival with stereotactic biopsy needle, resection cavity wall, and intravenous/cavity wall vector injection ranging from 12.1–13.6 months. Analysis of pretreatment resected tumor samples for mRNA expression patterns showed a survival-related signature that otherwise does not correlate with survival in publically available databases. Preliminary data from these studies supported initiation of a randomized, Phase 2/3 study in patients with rHGG (NCT02414165) in 2015. Updated and pooled safety data, immune response findings, and updated efficacy data for the Phase 1 studies will be presented.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.010 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".