A Phase I, Open-label, Single-arm, Multicentre Study to Evaluate the Safety and Pharmacokinetics of Tovorafenib in Japanese Paediatric Participants With BRAF-altered Recurrent or Progressive Low-grade Glioma
A Study to Assess a Medicine Called Tovorafenib in Japanese Children and Young Adults With Brain Tumours
Veramendi Susie
Ipsen Pharma SAS
Av. de Burgos 21 Torre C, 8a, Chamartin 28036 Madrid, Spain
+81-3-6205-6799
clinical.trials@ipsen.com
Rosario Chikako
Parexel International Inc.
Kayabacho Tower, 1-21-2, Shinkawa, Chuo-ku, Tokyo
+81-80-8929-3137
Clinicaltrial-registration@parexel.com
Recruiting
Mar. 11, 2026
Mar. 10, 2026
6
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
- Participants must be 6 months to 25 years of age, inclusive, with at least two generations of Japanese ancestry at the time of signing the informed assent/consent.
- Participants must have relapsed or progressive low-grade glioma with a documented known activating BRAF alteration, including BRAF V600 mutations and KIAA1549:BRAF fusions, as identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments-certified or other similarly certified laboratories.
- Participants must have histopathologic verification of malignancy at either original diagnosis or relapse.
- Participants must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression.
- Participants must have at least one evaluable and/or measurable lesion (imaging must be performed within 28 days of initiation of treatment) as defined by Response Assessment in Neuro-Oncology-high grade glioma criteria (T1 weighted lesion that can be reproducibly measured in at least two dimensions of at least 10 mm, visible on >=2 axial slices that are preferably, at most, 5 mm apart with 0 mm skip).
- Participants must have fully recovered from the acute toxic effects of all prior anticancer chemotherapy
- Chronic toxicities from prior anticancer therapy must be stable and at National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade =<2; ongoing retinopathy must be =<1.
- Participants must have adequate hematologic, hepatic and renal function
- Participants receiving steroids for tumour-associated symptoms must be on a stable dose (e.g. no initial/loading dose, no increase or decrease) for 14 days prior to C1D1.
- Participants must be able to swallow tablets or liquid or administer through gastric access via a feeding tube (12 Fr or greater).
- Participant's tumour has an additional previously known or expected to be activating molecular alteration(s) (e.g. histone mutation, isocitrate dehydrogenase 1 and 2 mutations, fibroblast growth factor receptor mutations or fusions, MYBL v-myb avian myeloblastosis viral oncogene homolog-like alterations, neurofibromatosis type-1 somatic or germline mutations).
- Participant has symptoms of clinical progression without radiographically recurrent or radiographically progressive disease.
- Participant has known or suspected diagnosis of neurofibromatosis type 1 via genetic testing or current diagnostic criteria.
- Participant has history of any major disease (e.g. confirmed or suspected diagnosis of interstitial lung disease), other than the primary malignancy under study, that in the opinion of the investigator might interfere with safe protocol participation.
- Participant has a history or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO), or ophthalmopathy present at baseline that would be considered a risk factor for CSR or RVO. Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) will NOT be considered significant abnormalities for the purposes of this study.
- Participant has major surgery within 14 days (2 weeks) prior to Cycle 1 Day 1 (does not include central venous access, cyst fenestration or cyst drainage, or ventriculoperitoneal shunt placement or revision).
- Participant has clinically significant active cardiovascular disease, history of myocardial infarction, deep vein thrombosis/pulmonary embolism within 6 months prior to C1D1, ongoing cardiomyopathy or current prolonged QT interval corrected for heart rate by Fridericia's formula interval >470 milliseconds based on triplicate electrocardiogram (ECG) average.
- Participant has nausea and vomiting NCI-CTCAE v5.0 Grade >=2, malabsorption requiring supplementation or significant bowel or stomach resection that would preclude adequate absorption of tovorafenib.
- Participant is neurologically unstable despite adequate treatment (e.g. uncontrolled seizures).
- Concomitant medications that are strong inhibitors or inducers of CYP2C8 within 14 days before initiation of therapy. Concomitant medications that are substrates of breast cancer resistance protein (BCRP) with a narrow therapeutic index within 14 days before initiation of therapy.
- Participant has any clinically significant skin toxicity at Screening that in the opinion of the investigator would increase risk of severe skin toxicity when using investigational product.
6month old over
25age old under
Both
Low-grade Glioma
Drug: Tovorafenib
Tablet or powder for reconstitution / powder for oral suspension, administered once weekly
1. Percentage of participants experiencing Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
[Time Frame: From first dose until 30 days post-treatment]
2. 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]
3. Area under the plasma concentration-time curve from time zero to last measurable concentration (AUC#-t) of tovorafenib following a single dose
AUC#-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)]
4. Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC#-inf) of tovorafenib following a single dose
AUC#-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)]
5. 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)]
6. 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)]
7. Terminal half-life (t1/2) of tovorafenib following a single dose
Terminal half-life (t1/2) 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)]
8. Area under the plasma concentration-time curve over the dosing interval at steady-state (AUC#-tau) of tovorafenib
AUC#-tau refers to the area under the plasma concentration-time curve over the dosing interval (tau) during steadystate 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)]
9. 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)]
10. 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)]
11. 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)]
12. 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 steadystate 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 third 28-day treatment cycle starting from Cycle 1 Day 1 until end of treatment]
