Ojemda (tovorafenib)

Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.

Assessment with green chemistry tools yielded favourable eco-scores (ComplexMoGAPI 90, AGREE 0.61, BAGI 70, RAPI 92.5, EVG Q2, and RGBfast 97.5%). This validated RP-UPLC procedure offers reliable, sensitive, and sustainable Tovorafenib analysis, supporting both efficient pharmaceutical quality control and environmental sustainability.

This review will highlight the molecular and genetic underpinnings of these tumors and how targeted therapeutic strategies led to the US Food and Drug Administration's approvals of combination therapy with dabrafenib and trametinib for pediatric patients with BRAF V600E mutant low-grade glioma; tovorafenib, a pan-RAF inhibitor, for pediatric BRAF mutant glioma; and vorasidenib, an inhibitor of mutant IDH1/2 enzymes, for patients with mutant IDH low-grade glioma. Integration of these targeted therapies into currently accepted treatment paradigms remains to be fully understood, along with the long-term impact on patient quality of life and prognosis.

P1/2, N=84, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Sep 2025 --> Jun 2026

P2, N=79, Not yet recruiting, Nationwide Children's Hospital

P2, N=23, Terminated, Day One Biopharmaceuticals, Inc. | Phase classification: P1/2 --> P2 | N=168 --> 23 | Active, not recruiting --> Terminated; Sponsor decision

Precision oncology is rapidly transforming the treatment landscape for rare CNS tumours. Integration of targeted therapies into clinical protocols - ideally guided by multidisciplinary molecular tumour boards - is increasingly warranted. Future research must optimise timing, combination strategies, and overcome resistance, while new biomarkers and liquid biopsy tools are needed to guide the choice of therapy and monitor response in this underserved population.

P1, N=44, Terminated, Day One Biopharmaceuticals, Inc.

P1/2, N=78, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Jun 2025 --> Sep 2025

This study provided potential prognostic biomarkers for LUAD and might facilitate the development of effective immunotherapy strategies for LUAD patients.

This case highlights the importance of tumor molecular characterization, particularly in rare tumors, whereby identification of the BRAF:KIAA1594 gene fusion led to an appropriate selection of a type II BRAF inhibitor.

P1, N=57, Recruiting, Daniel Morgenstern | Trial primary completion date: Mar 2026 --> Mar 2027