Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Tovorafenib · 3 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.
| 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. |
| Name | Type | Description |
|---|---|---|
| Tovorafenib | DRUG | Oral Tablet Powder for Oral Suspension |
| Chemotherapeutic Agent | DRUG | Intravenous solution for injection |
Inclusion Criteria: * Less than 25 years of age with LGG with known activating RAF alteration. * Histopathologic diagnosis of glioma or glioneuronal tumor. * At least one measurable lesion as defined by RANO criteria. * Meet indication for first-line systemic therapy. Exclusion Criteria: * Partic...
Tovorafenib is an investigational small molecule being studied for the treatment of pediatric low-grade glioma, craniopharyngioma, and advanced solid tumors. It is being evaluated in children and young adults with relapsed or progressive disease, as well as in those requiring first-line systemic therapy for low-grade glioma.
Tovorafenib is a RAF inhibitor that targets RAF1, BRAF, and ARAF. It is being studied in pediatric low-grade glioma and craniopharyngioma, where RAF pathway alterations are common. The drug is designed to inhibit these kinases, which are involved in cell growth and proliferation.
Tovorafenib is being developed by Day One Biopharmaceuticals, Inc., a company traded under the ticker DAWN. The company is conducting clinical trials to evaluate the drug in pediatric and young adult patients with low-grade glioma and craniopharyngioma.
Tovorafenib is in Phase 2 clinical development for low-grade glioma and craniopharyngioma. It has received FDA designations including Priority Review, Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease. The drug is investigational and has not been approved by the FDA.
Tovorafenib is being studied in two active Phase 2 trials: NCT04775485 for pediatric and young adult participants with relapsed or progressive low-grade glioma and advanced solid tumors, and NCT05465174 for craniopharyngioma in children and young adults. A Phase 3 trial, NCT05566795, is also active but not recruiting.
Tovorafenib is also known as DAY101. The Phase 3 trial NCT05566795, which compares DAY101 to standard of care chemotherapy in pediatric low-grade glioma, uses the DAY101 name. Both names refer to the same investigational drug.