Zidesamtinib (Jideytro) is an oral, brain-penetrant ROS1-selective inhibitor approved for adults with advanced ROS1-positive non-small cell lung cancer (NSCLC) previously treated with a ROS1 inhibitor.
Dose: 100 mg orally once daily for locally advanced/metastatic ROS1-positive NSCLC post-prior TKI therapy.
Mechanism & Efficacy: Overcomes resistance mutations like G2032R while sparing TRK inhibition; the ARROS-1 trial demonstrated a 44% response rate and activity in brain metastases.
Side Effects: Includes edema, peripheral neuropathy, constipation, fatigue, and dyspnea.
Indication: Used for patients whose cancer has progressed after previous ROS1-targeted therapy, such as lorlatinib or repotrectinib.
Brain Penetration: Designed to cross the blood-brain barrier to treat and control central nervous system (CNS) brain metastases.
Resistance Mutations: Highly active against treatment-emergent resistance mutations like ROS1 G2032R.
Clinical Response: The ARROS-1 clinical trial showed an overall objective response rate of 44% in pretreated patients.
Recommended Dose: 100 mg taken orally once daily, with or without food.
Common Side Effects: Frequently reported reactions include peripheral edema, peripheral neuropathy, constipation, fatigue, and dyspnea.
Potential risks for central nervous system reactions, QTc interval prolongation, interstitial lung disease, and embryo-fetal toxicity.