Abstract CT248: Zidesamtinib in patients with ROS1+ NSCLC previously treated with repotrectinib or taletrectinib

Abstract Introduction: Preclinical data indicates that the investigational ROS1 TKI zidesamtinib offers improved potency against ROS1, including ROS1 G2032R resistance mutation, brain penetrance and TRK selectivity over FDA-approved dual TRK/ROS1 TKIs repotrectinib and taletrectinib. Maximizing ROS1 activity in the clinical setting, including activity in the CNS, is essential to drive clinically meaningful responses to treatment. ARROS-1 is evaluating zidesamtinib in patients (pts) with advanced/metastatic ROS1+ NSCLC and other solid tumors. Here we report data in pts with NSCLC previously treated with repotrectinib or taletrectinib. Methods: Key study endpoints in the global, single arm, phase 1/2 ARROS-1 trial (NCT05118789) include objective response rate (ORR, RECIST v1.1 by BICR), duration of response (DOR), intracranial ORR (IC-ORR), and safety. This efficacy analysis included repotrectinib or taletrectinib previously-treated pts with ROS1+ NSCLC and measurable disease by BICR, treated with zidesamtinib 100 mg QD. Data cut-off: 22 Sep 2025. Results: At baseline, efficacy evaluable pts (results in Table) with prior repotrectinib (n=46) or taletrectinib (n=19) received a median of 2 prior ROS1 TKIs (range 1-4 for either) and 3 prior anticancer therapies (range 1-7 and 1-6, respectively); 63% and 53% received prior chemo. ROS1 resistance mutations by local or central testing were reported in 35% and 42%; active CNS disease in 46% and 53%. The safety profiles in these pt groups were consistent with what was previously reported in the overall pivotal TKI pretreated study population, including the avoidance of TRK or neurological adverse events (Drilon AE, et al. J Thorac Oncol. 2025;20(10)(Suppl 3):S3). Conclusions: The meaningful clinical activity presented here for zidesamtinib, including in pts with CNS disease and ROS1 G2032R resistance mutation, indicates that many ROS1+ NSCLCs remain ROS1-dependent beyond repotrectinib and taletrectinib. Citation Format: Geoffrey Liu, Alexander E. Drilon, Benjamin Besse, Gianluca Spitaleri, Jessica J. Lin, Byoung Chul Cho, Tatsuya Yoshida, Daniel Haggstrom, Steven Kao, Aurelie Swalduz, Misako Nagasaka, Benjamin J. Solomon, Lorenza Landi, Chiara Bennati, Elvire Pons-Tostivint, Christophe Dooms, A. J. van der Wekken, Saiama Waqar, Shirish Gadgeel, Chia-Chi Lin, Tetsuro Kondo, Hidetoshi Hayashi, Daniel Tan, Giulia Pasello, Matteo Duca, Luis G. Paz-Ares, Antonio Calles, Enriqueta Felip, Julien Mazieres, Adrianus Johannes de Langen, Alice T. Shaw, Jonathan W. Riess, Marina Garassino, Elaine Shum, Christina S. Baik, Jessica R. Bauman, D. Ross Camidge, Chien-Chung Lin, Gee-Chen Chang, Dong-Wan Kim, Myung-Ju Ahn, Ji-Youn Han, Kiichiro Ninomiya, Ryo Ariyasu, Ross Andrew Soo, Sanjay Popat, Jürgen Wolf, Maria Rosario García Campelo, Vivek A. Upadhyay, Stephen V. Liu. Zidesamtinib in patients with ROS1+ NSCLC previously treated with repotrectinib or taletrectinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT248.

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Cancer Research
Published
2026-04-17
DOI
https://doi.org/10.1158/1538-7445.am2026-ct248
Primary Topic
Lung Cancer Treatments and Mutations
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article

Abstract CT248: Zidesamtinib in patients with ROS1+ NSCLC previously treated with repotrectinib or taletrectinib

Ryo Ariyasu, Kiichiro Ninomiya, Vivek Upadhyay, Jessica R. Bauman et al.
Cancer Research
Lung Cancer Treatments and Mutations
article

Abstract CT248: Zidesamtinib in patients with ROS1+ NSCLC previously treated with repotrectinib or taletrectinib

Ryo Ariyasu, Kiichiro Ninomiya, Vivek Upadhyay, Jessica R. Bauman, Daniel Häggström, Ji‐Youn Han, D G Kim, A. de Langen, Ross Andrew Soo, Aurélie Swalduz, Stephen V. Liu, Sanjay Popat, M Duca, A Calles, Chiara Bennati, Julien Mazières, Lorenza Maria Landi, Gianluca Spitaleri, Byoung Chul Cho, A J Van Der Wekken, G Liu, Elaine Shum, Alice Tsang Shaw, Jonathan Wesley Riess, Giulia Pasello, D SW Shao-Weng Tan, M.R. García Campelo, B Solomon, Marina Garassino, Gee-Chen Chang, Chien-Chung Lin, Jessica J. Lin, Christophe Dooms, Luis G. Paz-Ares, Saiama Waqar, Myung-Ju Ahn, Chia-Chi Lin, Enriqueta Felip, Shirish Madhav Gadgeel, Jürgen Wolf, Misako Nagasaka, Tetsuro Kondo, Hidetoshi Hayashi, Alexander E. Drilon, Elvire Pons-Tostivint, D. Ross Camidge, Christina S. Baik, Benjamin Besse, Tatsuya Yoshida, Steven Kao
article en

Abstract

Abstract Introduction: Preclinical data indicates that the investigational ROS1 TKI zidesamtinib offers improved potency against ROS1, including ROS1 G2032R resistance mutation, brain penetrance and TRK selectivity over FDA-approved dual TRK/ROS1 TKIs repotrectinib and taletrectinib. Maximizing ROS1 activity in the clinical setting, including activity in the CNS, is essential to drive clinically meaningful responses to treatment. ARROS-1 is evaluating zidesamtinib in patients (pts) with advanced/metastatic ROS1+ NSCLC and other solid tumors. Here we report data in pts with NSCLC previously treated with repotrectinib or taletrectinib. Methods: Key study endpoints in the global, single arm, phase 1/2 ARROS-1 trial (NCT05118789) include objective response rate (ORR, RECIST v1.1 by BICR), duration of response (DOR), intracranial ORR (IC-ORR), and safety. This efficacy analysis included repotrectinib or taletrectinib previously-treated pts with ROS1+ NSCLC and measurable disease by BICR, treated with zidesamtinib 100 mg QD. Data cut-off: 22 Sep 2025. Results: At baseline, efficacy evaluable pts (results in Table) with prior repotrectinib (n=46) or taletrectinib (n=19) received a median of 2 prior ROS1 TKIs (range 1-4 for either) and 3 prior anticancer therapies (range 1-7 and 1-6, respectively); 63% and 53% received prior chemo. ROS1 resistance mutations by local or central testing were reported in 35% and 42%; active CNS disease in 46% and 53%. The safety profiles in these pt groups were consistent with what was previously reported in the overall pivotal TKI pretreated study population, including the avoidance of TRK or neurological adverse events (Drilon AE, et al. J Thorac Oncol. 2025;20(10)(Suppl 3):S3). Conclusions: The meaningful clinical activity presented here for zidesamtinib, including in pts with CNS disease and ROS1 G2032R resistance mutation, indicates that many ROS1+ NSCLCs remain ROS1-dependent beyond repotrectinib and taletrectinib. Citation Format: Geoffrey Liu, Alexander E. Drilon, Benjamin Besse, Gianluca Spitaleri, Jessica J. Lin, Byoung Chul Cho, Tatsuya Yoshida, Daniel Haggstrom, Steven Kao, Aurelie Swalduz, Misako Nagasaka, Benjamin J. Solomon, Lorenza Landi, Chiara Bennati, Elvire Pons-Tostivint, Christophe Dooms, A. J. van der Wekken, Saiama Waqar, Shirish Gadgeel, Chia-Chi Lin, Tetsuro Kondo, Hidetoshi Hayashi, Daniel Tan, Giulia Pasello, Matteo Duca, Luis G. Paz-Ares, Antonio Calles, Enriqueta Felip, Julien Mazieres, Adrianus Johannes de Langen, Alice T. Shaw, Jonathan W. Riess, Marina Garassino, Elaine Shum, Christina S. Baik, Jessica R. Bauman, D. Ross Camidge, Chien-Chung Lin, Gee-Chen Chang, Dong-Wan Kim, Myung-Ju Ahn, Ji-Youn Han, Kiichiro Ninomiya, Ryo Ariyasu, Ross Andrew Soo, Sanjay Popat, Jürgen Wolf, Maria Rosario García Campelo, Vivek A. Upadhyay, Stephen V. Liu. Zidesamtinib in patients with ROS1+ NSCLC previously treated with repotrectinib or taletrectinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT248.

Cancer ResearchVol. 86(8_Supplement)
Universidade da Coruña (ES), Hebron University (PS), Okayama Shoka University (JP), Fox Chase Cancer Center (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), University Medical Center Groningen (NL), Memorial Sloan Kettering Cancer Center (US), Washington University in St. Louis (US), Cornell University (US), Université Paris-Saclay (FR), Georgetown University Medical Center (US), Peter MacCallum Cancer Centre (AU), Institut Gustave Roussy (FR), Samsung Medical Center (KR), Princess Margaret Cancer Centre (CA), Seoul National University Hospital (KR), Henry Ford Hospital (US), Hospital General Universitario Gregorio Marañón (ES), Kanagawa Prefectural Hospital Organization (JP), Centre Hospitalier Universitaire de Nantes (FR), University of Chicago (US), National Cancer Centre Japan (JP), National Cancer Center (US), Fred Hutch Cancer Center (US), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Chris O’Brien Lifehouse (AU), Kindai University Hospital (JP), University of California, Irvine Medical Center (US), Okayama University Hospital (JP), Levine Cancer Institute (US), Hospital Universitario 12 De Octubre (ES), Chung Shan Medical University Hospital (TW), Centre Léon Bérard (FR), Istituto Oncologico Veneto (IT), Dana-Farber Cancer Institute (US), Royal Marsden Hospital (GB), Japanese Foundation for Multidisciplinary Treatment of Cancer (JP), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NL), China Medical University Hospital (TW), Vall d'Hebron Hospital Universitari (ES), Institut Claudius Regaud (FR), Covalent Associates (United States) (US), National Taiwan University Hospital (TW), University of Colorado Cancer Center (US), Global Cancer Institute (US), National Cancer Centre Singapore (SG), Chest Hospital, Ministry of Health and Welfare (TW), Complexo Hospitalario Universitario A Coruña (ES), Vince Lombardi Cancer Clinic (US), Tumori Foundation (US), National University Hospital (SG), University Hospital Cologne (DE), Osaka University Hospital (JP), Tokyo National Hospital (JP), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), National Cheng Kung University Hospital (TW), Instituto de Investigación Biomédica de A Coruña (ES), University of California Davis Medical Center (US), National Cancer Research Institute (GB), New York University (US), European Institute of Oncology (IT), University of California, Davis (US), University of Colorado Denver (US), Nantes Université (FR), KU Leuven (BE)
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Lung Cancer Treatments and Mutations
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