Zidesamtinib shows 94% response rate in TKI-naive advanced ROS1-positive lung cancer

New results from the global Phase I/II ARROS-1 trial indicate clinically meaningful activity with the investigational drug zidesamtinib in patients with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who had not previously received a tyrosine kinase inhibitor (TKI). The findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer, held in Seoul, Republic of Korea, on Sept. 14 at 10:45 a.m. Korea Standard Time. The data come from a first-in-human program evaluating zidesamtinib at a fixed dose of 100 mg once daily across a geographically diverse study population.

Among 94 efficacy-evaluable TKI-naive patients, the objective response rate by blinded independent central review was 94%, with 88 of the 94 patients experiencing a tumor response. Durability of these responses was also reported: the nine-month duration-of-response rate was 94%, and the 12-month duration-of-response rate was 86%. These duration-of-response figures describe the proportion of responding patients whose responses were maintained at the specified timepoints in this single-arm cohort, and they are based on the same efficacy-evaluable TKI-naive population assessed by blinded independent central review.

Zidesamtinib also demonstrated substantial intracranial activity in the subset of patients with central nervous system (CNS) metastases. Among 10 evaluable patients with CNS metastases, the intracranial objective response rate was 100%, including a 70% intracranial complete response rate. The nine-month intracranial duration-of-response rate was 100%, and the 12-month rate was 78%. Because this intracranial analysis rests on a small number of evaluable patients, the reported rates carry the uncertainty inherent to a 10-patient subset, and the trial results should be read with that denominator in mind.

The ARROS-1 trial is a global, single-arm, first-in-human study. Its Phase II cohort enrolled patients with locally advanced or metastatic ROS1-positive NSCLC who were naive to TKI therapy, although up to one prior line of chemotherapy and/or immunotherapy was permitted. Patients received zidesamtinib 100 mg once daily. Across all lines of therapy, 532 patients with ROS1-positive NSCLC received zidesamtinib at this dose, including 183 who were TKI-naive. The study population was geographically diverse, with 35% of patients enrolled in the Asia-Pacific region, 33% in Europe and 32% in North America.

The safety profile reported at the conference was consistent with previous reports of the drug, according to the presenting investigators. The most common treatment-related adverse events occurring in at least 15% of patients were peripheral edema (34%), increased weight (18%), increased blood creatine phosphokinase (18%), dysgeusia (17%) and increased aspartate aminotransferase (15%). Treatment-related adverse events led to dose reductions in 11% of patients and treatment discontinuation in 1%.

“Zidesamtinib demonstrated clinically meaningful activity in TKI-naive patients with ROS1-positive NSCLC, with a safety profile consistent with previous reports and low rates of dose reduction and discontinuation. The findings support continued investigation of zidesamtinib in earlier lines of therapy,” said Alexander Drilon, M.D., of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York City.

As a single-arm, first-in-human trial, ARROS-1 did not include a randomized comparator arm, so the reported response and duration-of-response rates describe the observed performance of zidesamtinib in this cohort rather than a measured advantage over other treatments. The Phase II cohort’s eligibility criteria allowed up to one prior line of chemotherapy and/or immunotherapy, meaning some TKI-naive patients in the analysis had received other anticancer therapy before enrolling, while none had previously taken a ROS1-directed TKI. The efficacy results were assessed by blinded independent central review, and the intracranial endpoints were restricted to the evaluable CNS metastasis subset described above.

The presentation at the IASLC 2026 World Conference on Lung Cancer forms part of a broader dataset in which 532 patients with ROS1-positive NSCLC have received zidesamtinib across all lines of therapy. Within that overall program, the TKI-naive group comprised 183 patients, of whom 94 were efficacy-evaluable in the reported analysis. The investigators stated that the findings support continued investigation of zidesamtinib in earlier lines of therapy, and the reported safety signals, led by peripheral edema in 34% of patients, were accompanied by dose reductions in 11% and treatment discontinuation in 1% of patients across the studied population.

Subject of Research: Zidesamtinib demonstrates 94% response rate in TKI-naive patients with advanced ROS1-positive NSCLC

Article Title: Zidesamtinib demonstrates 93% response rate in TKI-naive patients with advanced ROS1-positive NSCLC

Article References: Zidesamtinib demonstrates 93% response rate in TKI-naive patients with advanced ROS1-positive NSCLC. Original publication (Bibliographic details unavailable.)

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Keywords: Zidesamtinib, demonstrates, response, rate, TKI-naive, patients, advanced, ROS1-positive, NSCLC, scientific research