A Study to Assess a Medicine Called Tovorafenib in Japanese Children and Young Adults With Brain Tumours

NCT07441707 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CLIN-60310-450
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

Brief Summary

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. 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. 2.Treatment period (up to 24 months): All eligible participants will receive tovorafenib.
3. 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. 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.

Conditions

Low-grade Glioma

Keywords

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

Outcome Measures

Primary Outcomes (12)

• Percentage of participants experiencing Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)

  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.

  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.

  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.

  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

  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

  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.

  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

  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.

  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.

  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

  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

  From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)

Secondary Outcomes (1)

• Change in total tumor volume over time

  Every 12 weeks from Cycle 1 Day 1 up to end of treatment (approximately 24 months).

Study Arms (1)

Tovorafenib

EXPERIMENTAL

Tablet or powder for reconstitution / powder for oral suspension, administred once weekly

Drug: Tovorafenib

Interventions

Tovorafenib DRUG

Tablet or powder for reconstitution / powder for oral suspension

Also known as: Ojemda®

Tovorafenib

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (6)

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

MeSH Terms

Interventions

tovorafenib

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Central Study Contacts

Ipsen Clinical Study Enquiries

CONTACT

See e-mail; clinical.trials@ipsen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2026
• First Posted: March 2, 2026
• Study Start: March 3, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (6)