Dr Patel on How Zidesamtinib Data From ARROS-1 Compare With Taletrectinib Data From TRUST-I/TRUST-II in ROS1-Positive NSCLC

“The expectation with targeted lung cancer now isn’t what it used to be, where you live in months; it’s where you live years and live well for years.”

Shiven B. Patel, MD, MBA, FACP, an associate professor in the Division of Oncology, Department of Medicine, at the University of Utah School of Medicine and an investigator at Huntsman Cancer Institute, discussed findings from the phase 1/2 ARROS-1 trial (NCT05118789) evaluating zidesamtinib (Jideytro) in patients with ROS1-positive non–small cell lung cancer (NSCLC), as well as how the agent’s efficacy and safety profiles may compare with those of taletrectinib (Ibtrozi).

First-line data from the TKI-naive cohort of ARROS-1 were presented at the 2026 IASLC World Conference on Lung Cancer. Among 94 evaluable patients given zidesamtinib 100 mg once daily, the objective response rate (ORR) was 94% (95% CI, 87%-98%). At a median follow-up of 15.2 months (range, 1.1-30.5), the 12-month progression-free survival (PFS) rate was 90% (95% CI, 81%-95%). The FDA approved zidesamtinib in July 2026 for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who previously received a ROS1 TKI; the agent remains investigational in the first-line setting.

Cross-trial comparisons with taletrectinib are limited by differences in populations, sites, study designs, and eligibility criteria, Patel cautioned. In a pooled analysis of the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials, taletrectinib produced a confirmed ORR of 88.8% (95% CI, 82.8%-93.2%) and a median PFS of 45.6 months (95% CI, 29.0-not reached) in TKI-naive patients. Patel described the difference in ORR as modest and unlikely to reach statistical significance in a head-to-head trial. With high response rates anticipated from both agents, durability is the key consideration. Because response rates are approaching a ceiling, Patel noted that he expects differences in toxicity profiles to drive treatment selection unless a large difference in PFS emerges over time.

With respect to safety, the most common treatment-related adverse effects with zidesamtinib in the pooled safety population (n = 532) were peripheral edema (34%), weight increase (18%), increased blood creatine phosphokinase (18%), dysgeusia (17%), and increased aspartate aminotransferase (15%). These effects led to dose reductions in 11% and discontinuation in 1%. Patel described the safety profiles of zidesamtinib and taletrectinib as different rather than better or worse. The FDA approved taletrectinib in June 2025 for adults with locally advanced or metastatic ROS1-positive NSCLC. Because he reaches for taletrectinib first, Patel stated that he would rarely use it in the second line, except for patients who initially received a first-generation TKI. He tailors the choice to each patient’s lifestyle, goals of care, and comorbidities.

In the pretreated setting, most patients across trials had received an earlier-generation TKI, such as entrectinib (Rozlytrek) or crizotinib (Xalkori), and few had received repotrectinib (Augtyro) or taletrectinib, Patel noted. Data on sequencing next-generation TKIs remain limited, and resistance to these agents is still emerging. He would also consider adding chemotherapy while continuing a TKI for intracranial activity, although that approach has not been formally studied.

Looking ahead, Patel wants PFS durations of several years paired with minimal treatment-related toxicity so that patients can live for years with a high quality of life. So far, he said, the data are encouraging.