{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T11:22:45Z","timestamp":1792408965110,"version":"4.4.0"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Taletrectinib is an oral, potent, CNS-active, selective, next-generation ROS1 tyrosine kinase inhibitor (TKI). We report integrated efficacy and safety from registrational taletrectinib studies in\n                      <jats:italic toggle=\"yes\">ROS1<\/jats:italic>\n                      + non\u2013small cell lung cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>TRUST-I and TRUST-II were phase II, single-arm, open-label, nonrandomized, multicenter trials. Efficacy outcomes were pooled from TRUST-I and TRUST-II pivotal cohorts. The safety population comprised all patients treated with once-daily oral taletrectinib 600 mg pooled across the taletrectinib clinical program. The primary end point was independent review committee\u2013assessed confirmed objective response rate (cORR). Secondary outcomes included intracranial (IC)-ORR, progression-free survival (PFS), duration of response (DOR), and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>As of June 7, 2024, the efficacy-evaluable population included 273 patients in TRUST-I and TRUST-II. Among TKI-na\u00efve patients (n = 160), the cORR was 88.8% and the IC-cORR was 76.5%; in TKI-pretreated patients (n = 113), the cORR was 55.8% and the IC-cORR was 65.6%. In TKI-na\u00efve patients, the median DOR and median PFS were 44.2 and 45.6 months, respectively. In TKI-pretreated patients, the median DOR and median PFS were 16.6 and 9.7 months. The cORR in patients with G2032R mutation was 61.5% (8 of 13). Among 352 patients treated with taletrectinib 600 mg once daily, the most frequent treatment-emergent adverse events (TEAEs) were GI events (88%) and elevated AST (72%) and ALT (68%); most were grade 1. Neurologic TEAEs were infrequent (dizziness, 21%; dysgeusia, 15%) and mostly grade 1. TEAEs leading to discontinuations (6.5%) were low.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Taletrectinib showed a high response rate with durable responses, robust IC activity, prolonged PFS, favorable safety, and low rates of neurologic adverse events in TKI-na\u00efve and pretreated patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00275","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T16:02:03Z","timestamp":1743696123000},"page":"1920-1929","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":68,"title":["Taletrectinib in\n                    <i>ROS1<\/i>\n                    + Non\u2013Small Cell Lung Cancer: TRUST"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04919811","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04395677","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3296-423X","authenticated-orcid":true,"given":"Maurice","family":"P\u00e9rol","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, L\u00e9on B\u00e9rard Cancer Center, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1458-0064","authenticated-orcid":true,"given":"Nathan A.","family":"Pennell","sequence":"additional","affiliation":[{"name":"Cleveland 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5308-615X","authenticated-orcid":true,"given":"Misako","family":"Nagasaka","sequence":"additional","affiliation":[{"name":"University of California Irvine School of Medicine and Chao Family Comprehensive Cancer Center, Orange, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-0098","authenticated-orcid":true,"given":"Enriqueta","family":"Felip","sequence":"additional","affiliation":[{"name":"Vall d\u2019Hebron University Hospital, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwen","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 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