Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as DAY101, TAK580, AMG-2112819, BSK1369
Tovorafenib · 4 trials · 7 indications
ORR assessed per Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria by Independent Review Committee (IRC), and defined as the proportion of participants with overall confirmed response of complete response (CR), partial response (PR), or minor response (MR).
Progression-free survival is defined as the time of documented response until disease progression as defined by Response assessment in neuro-oncology criteria (RANO) criteria. PFS will be reported by overall group at 12 months.
Scores over time from the PedsQL 4.0 Generic Core physical function domain rating form, which have multidimensional child self-report and parent proxy report scales to assess health-related quality of life (QOL) in children, adolescents, and young adults ages 2 - 25 years will be reported. Physical functioning, is the sub-scale of interest for this protocol. Items on the physical functioning sub-scale are scored on a 5-point Likert scale with raw scores ranging from 0- 4. Items are reversed scored and linearly transformed to a 0-100 scale. If more than 50% of the items in the scale are missing, the Scale Scores should not be computed. Higher scores indicate a higher level of physical functioning
ORR is defined as percentage of participants with best overall confirmed response of complete response (CR) or partial response (PR) by the Response Assessment in Neuro-Oncology - high-grade glioma (RANO-HGG) criteria.
An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Determined by the treating investigator and measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or RANO-HGG criteria, as appropriate.
A DLT is defined as an AE assessed as at least possibly related to the study medication, which occurs during Cycle 1 (typically 28 days following the first dose of DAY101)
| Arm | Type | Description |
|---|---|---|
| Tovorafenib | EXPERIMENTAL | - |
| Investigator's choice of Standard of care therapy | ACTIVE_COMPARATOR | - |
| Group 1: Neoadjuvant Tovorafenib | EXPERIMENTAL | Participants with newly diagnosed craniopharyngioma will receive one (1) dose of Tovorafenib within 7 days +/- 2 days prior to planned biopsy or resection. At completion of biopsy or resection, participants having undergone biopsy only or sub-total (STR) or near-total resection (NTR) will continue on maintenance monotherapy of Tovorafenib given once weekly at the respected recommended phase 2 dose (RP2D). Participants having undergone a gross total resection (GTR) will enter into follow-up only and will be part of the exploratory cohort. |
| Group 2, Arm A: Neoadjuvant Tovorafenib | EXPERIMENTAL | Participants with recurrent craniopharyngioma will receive one (1) dose of Tovorafenib within 7 days +/- 2 days prior to planned biopsy or resection. At completion of biopsy or resection, participants having undergone biopsy only or STR or NTR will continue on maintenance monotherapy of Tovorafenib given once weekly at the respected RP2D. |
| Group 2, Arm B: Non-biopsy/resection participants | EXPERIMENTAL | Non-biopsy/resection participants with recurrent disease will receive monotherapy of Tovorafenib given once weekly at the respected RP2D. |
| Arm 1: Low-Grade Glioma | EXPERIMENTAL | Participants with recurrent or progressive low-grade glioma will receive 420 milligrams/meters square (mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline body surface area (BSA). |
| Arm 2: Low-Grade Glioma Expanded Access | EXPERIMENTAL | Participants with recurrent or progressive low-grade glioma will receive 420 mg/m\^2 of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA. |
| Arm 3: Advanced Solid Tumor | EXPERIMENTAL | Participants with advanced solid tumors will receive 420 mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA. |
| DAY101 (formerly TAK-580, MLN2480) BSA </= 1.5m^2 | EXPERIMENTAL | Phase I Part B BSA \</= 1.5m\^2 * Patients (\< 25 years) with radiographically recurrent or radiographically progressive non-hematologic malignancies (Central Nervous System (CNS) or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible with the exception of patients with NF1 * Study treatment cycle lasts 28 days, oral, once a week |
| DAY101 (formerly TAK-580, MLN2480) BSA > 1.5m^2 | EXPERIMENTAL | Phase I Part B BSA \> 1.5m\^2 * Patients (\< 25 years) with radiographically recurrent or radiographically progressive non-hematologic malignancies (Central Nervous System (CNS) or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible with the exception of patients with NF1 * Study treatment cycle lasts 28 days, oral, once a week |
| Name | Type | Description |
|---|---|---|
| Tovorafenib | DRUG | Oral Tablet Powder for Oral Suspension |
| Chemotherapeutic Agent | DRUG | Intravenous solution for injection |
| DAY101 | DRUG | 28 day cycle, oral, once per week |
Inclusion Criteria: * Less than 25 years of age with LGG harboring a documented known activating RAF alteration, as identified through molecular assays performed at Clinical Laboratory Improvement Amendments (CLIA) or other similarly certified laboratories. * Histopathologic diagnosis of glioma or ...
Tovorafenib is an investigational small molecule RAF inhibitor being developed by Day One Biopharmaceuticals for pediatric brain tumors. It is in clinical development for low-grade glioma and craniopharyngioma, two tumor types that can affect children and young adults. It is given as an oral therapy and has not been approved by the FDA.
Tovorafenib targets RAF kinases, specifically RAF1, BRAF, and ARAF. By inhibiting these kinases, it is designed to block RAF-driven signaling in tumors that carry RAF alterations. This mechanism underlies its development in RAF-altered pediatric low-grade glioma and in craniopharyngioma.
Tovorafenib is being developed by Day One Biopharmaceuticals, Inc., which trades on Nasdaq under the ticker DAWN. The company is running clinical programs in pediatric low-grade glioma and craniopharyngioma, including a Phase 3 study comparing tovorafenib with standard-of-care chemotherapy in first-line pediatric low-grade glioma.
Tovorafenib is in Phase 2 development for craniopharyngioma and relapsed or progressive low-grade glioma, and it is also being studied in a Phase 3 trial in first-line pediatric low-grade glioma. It remains investigational and is not FDA approved; the clinical program is ongoing across multiple countries.
Tovorafenib is being studied in NCT05566795, a Phase 3 trial comparing it with standard-of-care chemotherapy in pediatric low-grade glioma (FIREFLY-2), and in NCT05465174, a Phase 2 trial in children and young adults with craniopharyngioma. A third study, NCT04775485, is a Phase 2 trial in relapsed or progressive low-grade glioma and advanced solid tumors.
Tovorafenib is being studied for pediatric low-grade glioma, including RAF-altered tumors, both as first-line therapy versus standard-of-care chemotherapy and in relapsed or progressive disease. It is also in development for craniopharyngioma in children and young adults. These uses are investigational and not yet approved.