CTNI-30. LOGGIC/FIREFLY-2: A PHASE 3, RANDOMIZED TRIAL OF TOVORAFENIB VS. CHEMOTHERAPY IN PEDIATRIC PATIENTS WITH NEWLY DIAGNOSED LOW-GRADE GLIOMA HARBORING AN ACTIVATING RAF ALTERATION
Bibliographic record
Abstract
Abstract BACKGROUND Genomic alterations and dysregulation of RAF are the main oncogenic driver in almost all pediatric low-grade gliomas (pLGGs). About 50%‒60% of pLGGs harbor KIAA1549-BRAF fusion and 5%‒15% BRAF V600E mutation. No targeted therapy has received regulatory approval for either relapsed or newly diagnosed pLGG to date. Tovorafenib is an investigational, oral, selective, CNS-penetrant, small molecule, type II panRAF inhibitor. The registrational, phase 2 FIREFLY-1 (NCT04775485) study with tovorafenib in pediatric patients with recurrent/progressive LGG is currently ongoing. METHODS LOGGIC/FIREFLY-2 (EudraCT 2022-001363-27) is a registrational, randomized, multicenter, global (~100 sites across Australia, Canada, Egypt, Europe, New Zealand, Singapore, South Korea, Taiwan, and USA), phase 3 trial evaluating the efficacy, safety, and tolerability of tovorafenib vs. standard of care (SoC) chemotherapy in patients < 25 years old with LGG harboring a RAF-alteration and requiring first-line systemic therapy. Approximately 400 patients will be randomized 1:1 to receive oral tovorafenib, 420 mg/m2 ( ≤ 600 mg) weekly (tablet or liquid suspension for 26, 28-day cycles), or an investigator’s choice of SoC chemotherapy: COG-V/C regimen (60 weeks), SIOPe-LGG-V/C (81 weeks) regimen, or single-agent vinblastine (70 weeks). After completing 26 cycles tovorafenib, patients may continue tovorafenib or opt to enter a drug holiday at any point. Patients who progress in the SoC arm may receive tovorafenib. Patients who progress after stopping tovorafenib may be re-challenged. Primary endpoint is ORR based on RANO criteria, as determined by an independent radiology committee. Key secondary endpoints are progression-free survival and duration of response per RANO criteria, and ORR per RAPNO criteria. Other secondary endpoints include changes in neurological and visual function, and safety and tolerability. Exploratory objectives include quality of life and health utilization measures, molecular biomarker evaluation for treatment response and resistance, efficacy of tovorafenib after progression on chemotherapy and retreatment upon progression during drug holiday.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".