Pexidartinib is a medicinal product that is being developed for the treatment of adult patients with symptomatic tenosynovial giant cell tumour (TGCT). TGCT is also referred to as giant cell tumour of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS). TGCT is a rare, neoplasm derived from the thin layer of tissue that lines the joints and tendons leading to the formation of a mass. TGCT normally affects young adults of both sexes and is associated with severe morbidity and functional limitation. Surgery is currently the standard treatment although some cases of TGCT have a poorer likelihood of successful cure with surgery due to the high risk of recurrence. There are no current systemic treatment for symptomatic TGCT.
Pexidartinib belongs to a group of medicines known as tyrosine kinase inhibitors (TKI). It is given orally as a capsule and works by blocking a receptor called colony-stimulating factor-1 receptor (CSF1R) to which a protein called macrophage colony-stimulating factor (M-CSF) attaches. By attaching and blocking CSF1R, pexidartinib is expected to block the activity of M-CSF, preventing tumour growth and helping to delay the onset of the symptoms of the disease. If licensed, pexidartinib may offer the first systemic treatment option for adults with symptomatic TGCT which is associated with severe morbidity or functional limitations, and which is not amenable to improvement with surgery.
Selpercatinib is in clinical development for the treatment of metastatic RET fusion-positive non-small cell lung cancer (NSCLC). NSCLC is the most common type of lung cancer and at the metastatic stage the disease has already spread from the lungs to other sites. Around 2% of these patients will have tumours that contain fusion mutations in the RET gene. Cells in these tumour produce altered RET signalling receptors that allow uncontrolled cancer growth. Currently the only treatment options that attempt to inhibit RET fusion-positive tumour activity are nonselective multikinase inhibitors.