Zidesamtinib — Drug Monograph

Brand names: Jideytro

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Zidesamtinib is an oral, brain-penetrant, ROS1-selective tyrosine kinase inhibitor. It potently inhibits ROS1 fusion oncoproteins, including the G2032R solvent-front resistance mutation that limits earlier ROS1 TKIs, while sparing the structurally related tropomyosin receptor kinase (TRK) family. Avoiding TRK inhibition is intended to minimize the neurologic (dizziness, gait, cognitive) off-target toxicities seen with less selective ROS1/TRK inhibitors, and its CNS penetrance targets the frequent brain metastases in ROS1-driven NSCLC.

FDA Indications

• Locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) in adults who have received a prior ROS1 tyrosine kinase inhibitor (approved July 2026).

Common Side Effects

• Edema
• Peripheral neuropathy
• Constipation
• Fatigue
• Dyspnea
• Nausea

Clinical Pearl

Next-generation, brain-penetrant ROS1-selective TKI that retains activity against the G2032R solvent-front resistance mutation while sparing TRK, aiming to avoid the neurologic off-target toxicity of dual ROS1/TRK inhibitors (repotrectinib, entrectinib). Approval (July 2026) rests on the single-arm ARROS-1 trial (NCT05118789) in ROS1 TKI-pretreated patients (n=117): ORR 44% (95% CI 34–53) with 6- and 12-month DOR rates of 82% and 69%. Intracranial ORR was 48% (20% intracranial complete…

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