Where Zidesamtinib Fits in the ROS1+ NSCLC Treatment Landscape

Patients with ROS1-positive non–small cell lung cancer (NSCLC) now have more treatment options with the recently approved zidesamtinib (Jideytro; GSK), according to Estelamari Rodriguez, MD, MPH, of the University of Miami Sylvester Comprehensive Cancer Center.¹

On July 22, 2026, the FDA approved zidesamtinib, a novel, brain-penetrant, ROS1-selective inhibitor, for adults with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who have previously received at least 1 ROS1 tyrosine kinase inhibitor. The decision was based on data from the phase 1/2 ARROS-1 trial (NCT05118789). In part 2 of an interview with The American Journal of Managed Care^®, Rodriguez discussed where zidesamtinib fits in the evolving ROS1 treatment landscape.

She explained that ROS1-positive lung cancer was initially treated with crizotinib (Xalkori; Pfizer). Because the drug was not specifically designed for ROS1, patients can develop resistance mutations that cause treatment to stop working, Rodriguez said. Other agents, including repotrectinib (Augtyro; Bristol Myers Squibb) and lorlatinib (Lorbrena; Pfizer), have been associated with additional adverse effects.

That has left an unmet need for therapies that can overcome resistance without adding extra toxicity for these often younger patients, she noted. Rodriguez added that she currently selects taletrectinib as first-line therapy based on data from the TRUST trial (NCT07154706), describing it as an “excellent” next-generation ROS1 inhibitor with strong brain activity and durable responses.

Data from the ARROS-1 trial show zidesamtinib to be an effective salvage regimen for previously treated patients, positioning it as a second-line option with strong intracranial activity and a favorable toxicity profile. Frontline data for zidesamtinib had not been released at the time of the interview, but positive results were shared last month at the 2026 World Conference on Lung Cancer in Seoul, South Korea.² With these data, clinicians will need to determine how zidesamtinib compares with other frontline agents, Rodriguez said.

For this rare group of patients, more options mean clinicians can use more effective treatments up front to set patients on a path to better outcomes, she noted. That includes selecting treatments that patients can tolerate well enough to maintain quality of life while also treating and preventing central nervous system metastases, which can strongly affect survival.

Because Rodriguez’s institution participated in ARROS-1, she recalled previously treated patients who received zidesamtinib and were able to come off supplemental oxygen. She described these responses as much better than what chemotherapy would offer. For a patient whose disease is progressing, having a drug likely to produce a response is critical, Rodriguez said.

Rodriguez attributed these responses to the drug’s design. Zidesamtinib was developed to penetrate the brain and selectively target ROS1, including the G2032R solvent-front mutation commonly seen after treatment with first- and second-generation inhibitors.

“I think being able to overcome the resistance, being able to show that those responses happened fast, and that they were durable, is really critical for these patients,” she concluded.

References

1. McCormick B. FDA oks zidesamtinib as new option for resistant ROS1+ NSCLC. AJMC^®. July 22, 2026. Accessed October 6, 2026. https://www.ajmc.com/view/fda-approves-zidesamtinib-offering-new-option-for-resistant-ros1-positive-nsclc
2. GSK presents positive registrational data to potentially expand Jideytro (zidesamtinib) to first-line ROS1-positive non-small cell lung cancer. News release. GSK. September 14, 2026. Accessed October 6, 2026. https://www.gsk.com/en-gb/media/press-releases/gsk-presents-positive-registrational-data-to-potentially-expand-jideytro/