Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MLN2480, TAK-580, Tovorafenib, AMG-2112819, BSK1369
DAY101 · 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 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...
DAY101 is an investigational small molecule drug being developed by Day One Biopharmaceuticals, Inc. for low-grade glioma, a type of brain tumor. It is a kinase inhibitor that targets RAF and is in Phase 1 clinical development. It has not been approved by the FDA.
DAY101 is being studied for the treatment of low-grade glioma, a slow-growing brain tumor. It is an investigational therapy and has not been approved for any indication. The Phase 1 trial evaluated DAY101 in patients with low-grade glioma and other tumors.
DAY101 targets RAF, a kinase protein involved in cell signaling. By inhibiting RAF, DAY101 aims to interfere with pathways that drive tumor growth. This mechanism is being investigated in low-grade glioma and other tumors.
DAY101 is being developed by Day One Biopharmaceuticals, Inc., a biopharmaceutical company. The company's ticker symbol is DAWN. Day One focuses on developing therapies for pediatric cancer patients.
DAY101 is in Phase 1 clinical development. A Phase 1 trial has been completed. The drug remains investigational and has not been approved by the FDA for any indication.
DAY101 has been evaluated in a Phase 1 clinical trial, NCT03429803, titled 'DAY101 In Gliomas and Other Tumors.' The trial enrolled 44 patients with low-grade glioma and other tumors, was controlled, and has been completed. It was conducted in the United States.