On July 22, the U.S. Food and Drug Administration (FDA) approved zidesamtinib (Jideytro), a ROS1 selective inhibitor, for the treatment of adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor. The approval comes ahead of the original target action date of September 18, 2026, and follows the FDA's Breakthrough Therapy and Orphan Drug designations.
Zidesamtinib’s next-generation design aims to combine high target-selectivity, broad coverage of ROS1 resistance mutations, and blood–brain barrier penetration to address disease in the brain. It has displayed durable treatment responses and a tolerable profile. Together, these features aim to help patients maintain disease control for longer while reducing the treatment challenges that can emerge over time.
Approximately 50,000 people worldwide are diagnosed each year with ROS1-positive NSCLC, often nonsmokers in their 40s and 50s who could stay on treatment for several years.
ARROS-1
The approval of zidesamtinib is based on results from the global single-arm ARROS-1 phase I/II clinical trial (ClinicalTrials.gov identifier NCT05118789) in patients with advanced or metastatic ROS1-positive NSCLC who were previously treated with a ROS1 inhibitor. The study demonstrated meaningful and durable responses, including in patients with brain metastases and ROS1 resistance mutations. In the overall population (n = 117), the objective response rate was 44% (95% confidence interval [CI] = 34%–53%). Duration of response rates at 6 and 12 months were 82% and 69%, respectively.
The most common (occurring in ≥ 15% of patients) adverse reactions in the pooled safety population (n = 446) included edema, peripheral neuropathy, constipation, fatigue, and dyspnea.
Alexander Drilon, MD, ARROS-1 trial investigator and Chief of the Early Development Service at Memorial Sloan Kettering Cancer Center, said: “Despite advances in treatment, resistance mutations, disease progression in the brain, and treatment-related adverse events continue to create challenges for patients. The responses observed in ARROS-1, including in heavily pretreated patients, represent meaningful progress for people living with this disease.”
Janet Freeman-Daily, Co-Founder and President of The ROS1ders, said: "For patients, the goal is not just more time, but quality time to live life as normally as possible while on treatment. The ROS1-positive community is deeply invested in advancing care with treatments that are effective and tolerable. Today's approval gives patients and their doctors an important new option and represents meaningful progress for our community."
The U.S. Prescribing Information is available here.
Zidesamtinib continues to be studied in ARROS-1, including in first-line treatment for patients who have not previously received a ROS1 inhibitor.
