FDA approves zidesamtinib for ROS1 -positive non-small cell lung cancer

Regulatory approval: On July 22, 2026, the FDA approved zidesamtinib (Jideytro; Nuvalent) for adults with locally advanced or metastatic ROS1-positive NSCLC after at least one prior ROS1 tyrosine kinase inhibitor. Approval was supported by the single-arm ARROS-1 trial (N=117), with confirmed ORR 44% (95% CI, 34–53) by BICR. Key labeled risks include CNS adverse reactions, QTc prolongation, ILD/pneumonitis, and others.

FDA approval (July 22, 2026)

The FDA approved zidesamtinib (Jideytro; Nuvalent, Inc.) for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who have received at least one prior ROS1 tyrosine kinase inhibitor (TKI).

Supporting evidence: ARROS-1

Efficacy was evaluated in ARROS-1 (NCT05118789), a multicenter, single-arm, open-label, multi-cohort trial in previously treated locally advanced/metastatic ROS1-positive NSCLC.

  • Efficacy population: 117 patients (59 with one prior ROS1 TKI; 58 with ≥2 prior ROS1 TKIs, including lorlatinib, repotrectinib, and/or taletrectinib)
  • Primary measures: confirmed overall response rate (ORR) and duration of response (DOR) per RECIST v1.1, assessed by blinded independent central review (BICR)
  • Results (overall): ORR 44% (95% CI, 34–53); among responders, 82% had DOR ≥6 months and 69% had DOR ≥12 months
  • ORR by prior therapy: 49% (95% CI, 36–63) after one prior ROS1 TKI; 38% (95% CI, 26–52) after ≥2 prior ROS1 TKIs

Labeling highlights

Warnings/precautions include CNS adverse reactions, QTc prolongation, interstitial lung disease/pneumonitis, skeletal fractures, myalgia with creatine phosphokinase elevation, pancreatic toxicity, and embryo-fetal toxicity. Recommended dose: 100 mg orally once daily, with or without food, until progression or unacceptable toxicity.

The review used RTOR and the FDA Assessment Aid; the application was approved two months ahead of the FDA goal date. Zidesamtinib received orphan drug designation. Full prescribing information will be posted on Drugs@FDA.

Sources