Jideytro Produced a 94% Response Rate in TKI-Naïve ROS1-Positive NSCLC

GSK presented updated first-line data for zidesamtinib, marketed as Jideytro, at the 2026 World Conference on Lung Cancer (WCLC). In 94 efficacy-evaluable adults with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who had not previously received a ROS1 tyrosine kinase inhibitor (TKI), 88 patients responded to treatment, for an objective response rate (ORR) of 94%. 4

The results suggest substantial systemic and brain activity in this molecularly defined, uncommon form of lung cancer. But ARROS-1 is a single-arm phase 1/2 study—not a randomized comparison against existing first-line ROS1 therapies—so it cannot determine whether Jideytro is superior to other available options. 4

The key ARROS-1 findings

After a median follow-up of 15.2 months, blinded independent central review found an ORR of 94% (88 of 94; 95% confidence interval, 87%–98%). Fourteen patients, or 15%, achieved a complete response. 4

The time-to-event results were also immature but encouraging:

• 90% of patients were progression-free at 12 months.
• Median progression-free survival and median duration of response had not been reached at the analysis cutoff.
• Among responders, 94% remained in response at nine months and 86% remained in response at 12 months. 4

These results are clinically notable because ROS1-positive NSCLC can be difficult to control over time, particularly when cancer involves the central nervous system.

Activity in brain metastases

GSK reported intracranial activity in the 10 patients who had measurable brain metastases at baseline. All 10 had an intracranial response, and seven patients (70%) achieved complete radiographic clearance in the brain. The intracranial response rate at 12 months was 78%. 4

GSK also reported no central-nervous-system progression among patients without brain metastases at study entry. 4

The brain findings are important because the ability of a targeted therapy to control or prevent progression in the central nervous system can be a meaningful consideration in ROS1-positive NSCLC. Still, the small number of patients with measurable brain metastases means the estimate should be interpreted cautiously.

Who was included in the first-line analysis?

ARROS-1 is a global, single-arm, first-in-human phase 1/2 trial of zidesamtinib. The WCLC analysis focused on adults with locally advanced or metastatic ROS1-positive NSCLC who had not received a prior ROS1 TKI. Patients could have received up to one previous line of chemotherapy and/or immunotherapy before entering the study. 4

In the efficacy-evaluable cohort:

• 27% had previously received chemotherapy.
• 17% had received both chemotherapy and immunotherapy.
• 17% had central-nervous-system metastases at baseline by blinded independent review. 4

That means “TKI-naïve” did not necessarily mean treatment-naïve: some participants had received earlier systemic treatment, but none had received a ROS1-targeted TKI.

Safety and treatment discontinuation

The most commonly reported treatment-related adverse events were peripheral edema, weight gain, increased creatine phosphokinase, altered taste and increased aspartate aminotransferase. GSK characterized these events as mostly low grade. 4

Dose reductions due to treatment-related adverse events occurred in 11% of patients, while 1% discontinued treatment because of a treatment-related adverse event. 4

Safety results from a relatively small, nonrandomized cohort require longer follow-up and broader clinical use to fully characterize tolerability. Nonetheless, the low discontinuation rate was part of GSK’s rationale for positioning the drug as a potential first-line option.

How does Jideytro compare with crizotinib and entrectinib?

Crizotinib and entrectinib are established first-line ROS1-targeted options. GSK highlighted zidesamtinib’s response rate, tolerability profile and reported activity in brain metastases as potentially differentiating features. 4

However, ARROS-1 did not randomly assign patients to zidesamtinib versus crizotinib, entrectinib or another comparator. Differences in enrolled patients, follow-up and assessment methods can make cross-trial comparisons misleading. The 94% ORR is therefore a strong signal of activity, not proof that Jideytro outperforms other first-line ROS1 therapies.

Why the ROS1-positive population matters

GSK estimates that ROS1 alterations occur in approximately 2% of NSCLC, or roughly 50,000 new ROS1-positive NSCLC diagnoses worldwide each year. The disease is often identified in younger people and nonsmokers and has a substantial tendency to spread to the brain. 4

Because ROS1-positive disease is uncommon, molecular testing is central to identifying patients who may be candidates for ROS1-directed treatment.

FDA status and GSK’s first-line plan

On July 22, 2026, the FDA approved Jideytro for adults with locally advanced or metastatic ROS1-positive NSCLC that had previously been treated with a ROS1 TKI. That approval was based on a separate ARROS-1 population of 117 previously treated patients, where the ORR was 44% (95% CI, 34%–53%). 13

GSK has said zidesamtinib received FDA orphan-drug and breakthrough-therapy designations in this disease setting. 4 At the time of the WCLC presentation, Jideytro was not approved for first-line treatment. GSK said it intended to submit a supplemental new drug application later in 2026 to seek an expanded indication for TKI-naïve patients. 14

Bottom line

The WCLC presentation put a clear number on GSK’s first-line case for Jideytro: a 94% objective response rate, including 14 complete responses, in 94 TKI-naïve patients with advanced ROS1-positive NSCLC. The complete intracranial responses observed in seven of 10 evaluable patients with brain metastases add to the interest in the program. 4

The next question is regulatory and comparative: whether the FDA expands the label to first-line use, and whether longer follow-up or comparative evidence can clarify Jideytro’s place alongside existing ROS1-targeted therapies.