Plixorafenib - A Novel Therapy Introduced for the Treatment of High-Grade Glioma
FORE Biotherapeutics has introduced plixorafenib for the treatment of adult patients with BRAF V600E-mutated high-grade glioma (HGG), an aggressive form of brain cancer associated with poor outcomes and limited treatment options.
Plixorafenib is an investigational BRAF inhibitor designed to selectively target BRAF alterations. The therapy has demonstrated anti-tumour activity in patients with BRAF-mutated central nervous system (CNS) tumours and is being evaluated as a potential treatment for several BRAF-altered cancers.
Plixorafenib has previously received Fast Track Designation for cancers harbouring BRAF Class 1 and Class 2 alterations, as well as Orphan Drug Designation for primary brain and CNS malignancies. These regulatory designations support the continued development of the therapy for patients with BRAF-altered tumours.
The designation is supported by data from a completed Phase 1/2a study and the ongoing Phase 2 FORTE basket trial involving patients with BRAF V600E-mutated CNS tumours. Clinical findings showed encouraging response rates and durable anti-tumour activity in patients with primary CNS tumours, including high-grade gliomas.
High-grade gliomas are aggressive primary brain tumours that can rapidly grow and spread within the brain. Patients often face limited survival prospects despite surgery, radiotherapy and chemotherapy. BRAF V600E mutations are recognised as important drivers of tumour growth in a subset of gliomas, making them a promising target for precision therapies. However, effective treatment options for recurrent or progressive disease remain limited, highlighting a significant unmet medical need.
The ongoing global Phase 2 FORTE basket study is evaluating plixorafenib across several BRAF-altered tumour types, including recurrent or progressive primary CNS tumours, solid tumours with BRAF fusions and rare BRAF V600-mutated solid tumours. Interim analyses from the CNS tumour cohort have supported the continued advancement of the study.
