Nuvalent, a biopharmaceutical company in the clinical stage, has declared that the U.S. Food and Drug Administration (FDA) has accorded breakthrough therapy designation (BTD) to NVL-520 for treating individuals with ROS1-positive metastatic non-small cell lung cancer (NSCLC). These patients should have undergone prior treatment with two or more ROS1 tyrosine kinase inhibitors (TKIs). ROS1 rearrangements are present in approximately 3% of metastatic NSCLCs. At the time of diagnosis, around 40% of these patients exhibit brain metastases, and roughly 40% develop resistance mutations after initial treatment.
Currently, there is no established standard of care for individuals previously treated with two or more ROS1 TKIs. NVL-520 is an innovative ROS1-selective tyrosine kinase inhibitor designed to penetrate the brain, addressing challenges such as emergent treatment resistance, brain metastases, and adverse events in the central nervous system (CNS) associated with inhibiting the tropomyosin receptor kinase (TRK) family.
The FDA's grant of breakthrough therapy designation recognizes the ongoing need for innovation in treating ROS1-positive NSCLC patients who have exhausted available therapies.NVL-520, as a novel brain-penetrant ROS1-selective inhibitor, seeks to overcome limitations observed in existing ROS1 inhibitors. It is engineered to remain effective in tumors resistant to current ROS1 inhibitors, including those with treatment-emergent ROS1 mutations like G2032R. Furthermore, NVL-520 is designed for CNS penetrance to enhance treatment options for patients with brain metastases, while avoiding inhibition of the structurally-related TRK family.
These characteristics aim to minimize TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and provide durable responses for patients across all therapy lines. NVL-520 has already received orphan drug designation for ROS1-positive NSCLC and is currently under investigation in the ARROS-1 trial (NCT05118789), a Phase 1/2 clinical trial for advanced ROS1-positive NSCLC and other solid tumors.
