Tovorafenib for Japanese children and young adults with BRAF‑altered low-grade brain tumours

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

This trial will test whether weekly oral tovorafenib is safe, how the body handles it, and if it can shrink BRAF‑altered low-grade brain tumours in Japanese children and young adults.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 6 Months to 25 Years
• Sex: All
• Sponsor: Ipsen (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 6 sites (Kanagawa and 5 other locations)
• Trial ID: NCT07441707 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label trial gives all eligible participants once-weekly oral tovorafenib to measure safety, pharmacokinetics, and preliminary anti-tumour activity in Japanese patients aged 6 months to 25 years with relapsed or progressive BRAF‑altered low-grade glioma. Eligibility requires documented activating BRAF alterations (including BRAF V600 mutations or KIAA1549:BRAF fusions), prior systemic therapy, and at least one measurable lesion. The protocol includes a screening period (up to 4 weeks) and a treatment period of up to 24 months with intensive visits during the first two cycles and monthly visits thereafter. Tumour response will be monitored by imaging and safety by clinical and laboratory assessments while pharmacokinetic sampling characterizes absorption, distribution, and elimination.

Who should consider this trial

Good fit: Children, adolescents, and young adults aged 6 months to 25 years of Japanese ancestry with relapsed or progressive low‑grade glioma and a documented activating BRAF alteration who have received at least one prior systemic therapy are the intended participants.

Not a fit: Patients without a documented activating BRAF alteration, those not meeting the Japanese ancestry requirement, those without measurable disease, or those with tumour types other than low‑grade glioma are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, tovorafenib could provide a targeted, once‑weekly oral option that shrinks or controls BRAF‑altered low‑grade gliomas in young patients.

How similar studies have performed: Other BRAF‑targeted therapies have shown benefit in BRAF‑mutant pediatric low‑grade glioma, and early data for tovorafenib and related RAF inhibitors are promising but still limited.

Eligibility criteria

Inclusion Criteria

* 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).

Exclusion Criteria

* 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.

Where this trial is running

Kanagawa and 5 other locations

• Kanagawa Children's Medical Center — Kanagawa, Japan (Not_yet_recruiting)
• Hyogo Prefectural Kobe Children's Hospital — Kobe, Japan (Recruiting)
• Kyoto University Hospital — Kyoto, Japan (Recruiting)
• Osaka City General Hospital — Osaka, Japan (Recruiting)
• National Cancer Center Hospital — Tokyo, Japan (Recruiting)
• National Center for Child Health and Development — Tokyo, Japan (Recruiting)

Study contacts

• Study coordinator: Ipsen Clinical Study Enquiries

Conditions Low-grade Glioma; BRAF-altered Recurrent Low-grade Glioma; Progressive Low-grade Glioma