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Zidesamtinib, an investigational next-generation ROS1 tyrosine kinase inhibitor (TKI) designed to be extremely selective, brain-penetrant, and TRK-sparing, demonstrated clinically significant exercise and sturdiness in sufferers with ROS1-positive (ROS1+) non-small cell lung most cancers (NSCLC) who had progressed on prior TKI remedy.
ROS1-positive NSCLC happens in roughly 1–2% of all NSCLC circumstances.
The outcomes from the Section I/II ARROS-1 trial had been introduced on the Worldwide Affiliation for the Examine of Lung Most cancers (IASLC) 2025 World Convention on Lung Most cancers (WCLC) by Dr. Alexander Edward Drilon of Memorial Sloan Kettering Most cancers Heart, New York Metropolis.
The worldwide, single-arm ARROS-1 trial (NCT05118789) enrolled sufferers with superior or metastatic ROS1+ NSCLC. The pivotal evaluation included TKI pre-treated sufferers with measurable illness who began zidesamtinib 100 mg as soon as each day by Could 31, 2024.
Preliminary knowledge had been additionally collected from TKI-naive sufferers handled by August 31, 2024. Key endpoints included goal response charge (ORR) by blinded impartial central overview (BICR), period of response (DOR), intracranial ORR (IC-ORR), and security. Information cutoff was March 21, 2025.
A complete of 432 sufferers (36% Asia-Pacific, 32% North America, 32% Europe) acquired zidesamtinib at 100 mg as soon as each day. Among the many 117 efficacy-evaluable TKI pre-treated sufferers, median prior therapies had been two, with 50% having acquired two or extra prior ROS1 TKIs and 93% uncovered to lorlatinib, repotrectinib, and/or taletrectinib. CNS illness was current in 49% of sufferers.
Sturdy responses had been noticed in TKI pre-treated sufferers, together with in these with CNS involvement, ROS1 G2032R mutations, and people with a number of prior ROS1 TKIs.
Any TKI pre-treated (n = 117): ORR of 44%, with a 12-month DOR charge of 78%.
Prior crizotinib or entrectinib solely (n = 55): ORR of 51%, with a 12-month DOR charge of 93%.
Preliminary knowledge had been reported for 35 TKI-naive sufferers:
TKI-naive sufferers (n=35): ORR of 89%, with a 12-month DOR charge of 96%.
Intracranial exercise: IC-ORR of 83%, together with 4 full responses; no CNS development occasions at knowledge cutoff.
Zidesamtinib was usually effectively tolerated and the commonest treatment-emergent opposed occasions (TEAEs; ≥15% of sufferers) included peripheral edema (36%), constipation (17%), creatine phosphokinase (CPK) enhance (16%), fatigue (16%), and dyspnea (15%). Grade ≥3 occasions had been rare. Dose reductions occurred in 10% of sufferers and remedy discontinuations in 2%.
“Zidesamtinib’s highly selective, brain-penetrant, TRK-sparing design allowed for meaningful disease control in patients who had exhausted available options,” mentioned Dr. Drilon. “The promising preliminary results in TKI-naive patients also support further development.”
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Worldwide Affiliation for the Examine of Lung Most cancers
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Zidesamtinib exhibits sturdy responses in ROS1 TKI pre-treated NSCLC (2025, September 7)
retrieved 7 September 2025
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