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.
Selpercatinib is a first-in-class oral precision cancer medicine designed to selectively bind to cancers that harbour genetic abnormalities in the RET proteins. This binding inhibits the RET receptor signalling which in turn inhibits the tumour cell growth and may also prevent resistance to the treatment from developing. Selpercatinib is being developed for NSCLC and other advanced solid tumours with RET genetic alterations with early results indicating significantly improved outcomes. If licensed, selpercatinib will offer a first-in-class treatment option for RET-fusion positive NSCLC, who currently have no highly selective therapies available.
Durvalumab is in development for patients with advanced/metastatic non-small cell lung cancer (NSCLC) who are EGFR/ALK wild-type and whose tumours have a high PD-L1 expression. NSCLC makes up the majority of lung cancers in the UK. Advanced/metastatic (Stage IV) NSCLC is when the cancer has spread beyond the lung which was initially affected, most often to the liver, the adrenal glands, the bones and the brain. Most patients with NSCLC are diagnosed at the advanced/metastatic stage where curative treatment with surgery is unsuitable. Currently, chemotherapy remains the first line treatment option but this is often not well tolerated by many patients.