Company: DAWN
Filing Date: 2025-02-25
Form Type: 10-K
Source: 0000950170-25-026654
Chunk: 75

Company: Day One Biopharmaceuticals, Inc.
Filing Date: 2025-02-25
Form: 10-K
Item: Item 1
Chunk 75
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GGs have tumors with a BRAF V600E activating mutation.  

With the exception of the combination of dabrafenib-trametinib for patients >6 years of age with relapsed/progressive tumors bearing a BRAF V600E/K mutation, there have been no agents approved for use in this population and as such, are only available via clinical trials or off-label prescription. Off-label use, while common in the pediatric oncology setting, is recognized to be an inferior approach as it exposes children to potential risks without the associated safeguards that accompany comprehensive clinical development activities, such as long-term safety monitoring and pharmacovigilance activities. We believe that the intentional development of a specifically-targeted, brain-penetrant therapy for pLGG is essential to improve outcomes for these patients, particularly those with BRAF fusions, and patients with BRAF V600E mutations who are either <6 years of age or who have progressed on, or cannot tolerate, combined Type I RAF/MEK inhibition.

Clinical trial results for pLGG

Tovorafenib is currently being evaluated in an ongoing investigator-initiated, multi-center study (PNOC014, NCT03429803) in patients with relapsed or refractory gliomas (high- and low-grade) and other tumors that is being conducted by Dana-Farber Cancer Institute in collaboration with PNOC. The trial remains open but is closed to new patient accrual. As of June 2023, a total of 44 patients had been enrolled in Part B of this Phase 1 dose-escalation trial (9 patients in Part A, 35 patients in Part B), which was conducted at multiple institutions within the PNOC network. Once-weekly tovorafenib at doses as high as 420 mg/m2/week were well-tolerated in patients ≥ 1.5m2, while doses as high as 530 mg/m2/week were found to be well-tolerated in patients < 1.5m2. Data was presented at the 2022 Society for Neuro-Oncology meeting for the 35 patients studied in Part B. For this group, there were two complete responses, seven partial responses, fifteen patients with stable disease and eight patients who had progressive disease. There were six dose limiting toxicities, all at 530 mg/m2/week, all Grade 3, and five known side effects (two fatigue, three rash, one menorrhagia). 

As shown in