Individuals diagnosed with ROS1-positive non–small cell lung cancer (NSCLC) now have more treatment options, thanks to the recent approval of zidesamtinib (Jideytro; GSK), as highlighted by Estelamari Rodriguez, MD, MPH, from the University of Miami Sylvester Full Cancer Center.
On July 22, 2026, the FDA approved zidesamtinib for adult patients with locally advanced or metastatic ROS1-positive NSCLC who have previously undergone treatment with at least one ROS1 tyrosine kinase inhibitor. This decision was supported by findings from the phase 1/2 ARROS-1 trial.
Treatment Environment
Rodriguez noted that crizotinib (Xalkori; Pfizer) was the initial therapy for ROS1-positive lung cancer, but resistance mutations often render it ineffective over time.
Alternative treatments, such as repotrectinib (Augtyro; Bristol Myers Squibb) and lorlatinib (Lorbrena; Pfizer), have been linked to additional side effects, leaving a critical need for therapies that address resistance without increasing toxicity.
Zidesamtinib’s Position
Rodriguez currently favors taletrectinib as the initial treatment, citing data from the TRUST trial that demonstrates its effectiveness as a next-generation ROS1 inhibitor with robust brain activity and sustained responses.
Results from the ARROS-1 trial indicate that zidesamtinib serves as a valuable option for patients who have already received prior treatment, offering strong intracranial activity and a manageable side effect profile.
With the availability of first-line data for zidesamtinib, clinicians will need to assess how it compares to other initial treatment options, according to Rodriguez.
Patient Impact
She shared examples of previously treated patients who, after receiving zidesamtinib, were able to discontinue supplemental oxygen, noting that these outcomes far surpass what chemotherapy typically achieves.
Rodriguez described taletrectinib as an “excellent” next-generation ROS1 inhibitor with strong brain activity and durable responses. Zidesamtinib was developed to penetrate the brain and selectively target ROS1, including the G2032R solvent-front mutation often observed after treatment with earlier-generation inhibitors.