Entrectinib is in clinical development for the oral treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with ROS1 genetic rearrangement. NSCLC makes up the majority of lung cancer cases and can be classified according to how far the cancer has spread. Stage III, or locally advanced NSCLC is when the cancer has spread within the lungs and surrounding areas. Stage IV NSCLC is when the cancer has spread to other locations and organs within the body. Many different factors can increase the risk of developing NSCLC, including certain genetic changes, such as changes to the ROS1 gene which lead to increased levels of the ROS1 protein. Increased levels of ROS1 have been found in many different types of cancer, including NSCLC, and are thought to contribute to the development of cancer.
Entrectinib is a drug that specifically targets and blocks the ROS1 protein overproduced in many types of cancers including NSCLC. Preclinical trials suggest it may be more potent in targeting ROS1 than the currently approved therapy crizotinib. If licenced entrectinib would provide an additional specific treatment option for patients with ROS rearranged, locally advanced or metastatic NSCLC.
Nivolumab is a type of immunotherapy that is currently licensed in the UK for the treatment of several types of advanced cancers such as melanoma, non‐small cell lung cancer, and kidney cancer. It blocks a protein called programmed death-1 (PD-1), which is found on the surface of a type of immune cells called T-cells. Blocking PD-1 stimulates the T-cells to kill the cancer cells. Temozolomide in combination with radiotherapy is currently licensed in the UK for newly diagnosed glioblastoma in adults. The addition of nivolumab to temozolomide and radiotherapy will potentially offer an additional first line treatment option for adult patients who are newly diagnosed MGMT-methylated glioblastoma.