The purpose of this study is to evaluate safety and the way the body absorbs, distributes and gets rid of the study drug tovorafenib in the body in Japanese children, adolescents and young adults with specific brain tumours. This includes how the drug is absorbed, distributed and eliminated from the body (called pharmacokinetics). The study will also test how well the drug works to shrink brain tumours. In this study, all participants will receive tovorafenib orally once weekly. There will be four periods in this study: 1. Screening period (up to 4 weeks): Participants will be evaluated to determine if they can take part in the study, requiring at least one visit to the study centre. 2. Treatment period (up to 24 months): All eligible participants will receive tovorafenib. This requires five visits for the first 2 months (Cycle 1 and Cycle 2) followed by one visit every month (at the start of each treatment cycle). Participants will receive the first oral dose of tovorafenib on Day 1 of Cycle 1 at the study clinic. After Day 1, participants will need to take tovorafenib once weekly on Day 8, Day 15 and Day 22. Participants will be required to come to the study clinic in person at least five times for Cycle 1 and Cycle 2. In addition, participants will have one remote visit (telephone call) during Cycle 1. After Cycle 2, only one in-person clinic visit is required at the start of each treatment cycle. A participant will stop treatment if their disease gets worse, if treatment has a harmful effect, or if they do not want to take part in the study anymore. 3. End-of-Treatment Safety Follow-Up (30 days): Participants will have a clinic visit 30 days after stopping treatment to check their health. 4. Long-Term Follow-Up (up to 2 years): Participants will be monitored every 3 months unless they start a new anti-cancer treatment or leave the study. During the study, participants will undergo various health measurements and observations, including blood sampling and urine collections. Each participant will be in this study for up to approximately 4 years. Tovorafenib will be provided to participants who tolerate it for as long as their disease does not progress. Once tovorafenib becomes approved and commercially available in Japan, participants may transition to the commercial drug for continued treatment. A participant may withdraw consent to participate at any time.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Tablet or powder for reconstitution / powder for oral suspension
Percentage of participants experiencing Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
Time frame: From first dose until 30 days post-treatment
Percentage of participants experiencing Serious Adverse Events (SAEs) and AESIs
An Adverse event (AE) is any untoward medical occurrence, temporally associated with the use of study intervention, whether or not related to the study intervention.
Time frame: Up to 4 years from first dose, including post-treatment monitoring
Area under the plasma concentration-time curve from time zero to last measurable concentration (AUC₀-t) of tovorafenib following a single dose
AUC₀-t represents the total drug exposure over time from administration until the last measurable concentration after a single dose of tovorafenib.
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC₀-inf) of tovorafenib following a single dose
AUC₀-inf estimates the total drug exposure from administration to infinite time, extrapolating beyond the last measurable concentration.
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Maximum observed plasma concentration (Cmax) of tovorafenib following a single dose
Cmax is the highest concentration of tovorafenib observed in plasma after a single dose
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Time to maximum plasma concentration following a single dose (Tmax) of tovorafenib
Tmax refers to the time point at which the maximum observed plasma concentration of tovorafenib is reached following a single dose
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Terminal half-life (t½) of tovorafenib following a single dose
Terminal half-life (t½) will be assessed following a single dose of tovorafenib.
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Area under the plasma concentration-time curve over the dosing interval at steady-state (AUC₀-tau) of tovorafenib
AUC₀-tau refers to the area under the plasma concentration-time curve over the dosing interval (tau) during steady-state conditions, representing total drug exposure per dosing cycle
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Maximum plasma concentration at steady-state (CmaxSS) of tovorafenib
CmaxSS refers to the maximum observed plasma concentration of tovorafenib measured during steady-state conditions, after repeated dosing when drug input and elimination have reached equilibrium.
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Minimum plasma concentration at steady-state (CminSS) of tovorafenib
CminSS refers to the lowest observed plasma concentration of tovorafenib during steady-state conditions, reflecting trough levels between doses.
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Average Plasma Concentration at Steady-State (CavSS) of tovorafenib
CavSS refers to the average plasma concentration of tovorafenib over the dosing interval during steady-state conditions, calculated from multiple time points
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Time to maximum plasma concentration at steady-state (TmaxSS) of tovorafenib
TmaxSS refers to the time point at which the maximum plasma concentration of tovorafenib is observed during steady-state conditions
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)
Change in total tumor volume over time
Assessment based on MRI imaging data to evaluate tumor volume and its evolution during treatment.
Time frame: Every 12 weeks from Cycle 1 Day 1 up to end of treatment (approximately 24 months).
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