{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:21:00Z","timestamp":1789770060459,"version":"4.0.1"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      To evaluate the safety and efficacy of izalontamab brengitecan (iza-bren) in patients with non\u2013small cell lung cancer (NSCLC) harboring actionable genomic alterations (GAs) outside of classical epidermal growth factor receptor (\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      ) mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Eligible patients had locally advanced or metastatic NSCLC with prespecific actionable GAs, had progressed after standard treatment and received no more than one previous line of chemotherapy. iza-bren was administered at the dose of 2.5 mg\/kg once per day on days 1 and 8 of each 3-week cycle. The primary end point was safety. The secondary end points included objective response rate (ORR), disease control rate (DCR), and duration of response. The exploratory end points included progression-free survival (PFS) and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A total of 83 patients with NSCLC were enrolled in four cohorts:\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      exon20ins\/nonclassical mutations (n = 14), human epidermal growth factor receptor 2 (\n                      <jats:italic toggle=\"yes\">HER2<\/jats:italic>\n                      ) mutation (n = 19),\n                      <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">MET<\/jats:italic>\n                      mutation (n = 26), and\n                      <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">ROS1<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      fusion (n = 24). The most common grade \u22653 treatment-related adverse events (TRAEs) were thrombocytopenia (51.8%), anemia (44.6%), and neutropenia (43.4%). The most frequent nonhematologic TRAEs of all grades were nausea (49.4%), asthenia (45.8%), stomatitis (44.6%), and diarrhea (38.6%). One case of grade 2 interstitial lung disease was observed. The confirmed ORR was 39.7%, and the DCR was 85.9%. The median PFS was 7.0 months (95% CIs, 5.4 to 10.5), while OS data were immature. Patients with\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      exon20ins or other nonclassical mutations achieved an ORR of 69.2% with a median PFS of 10.5 months (95% CI, 6.9 to not reached); the\n                      <jats:italic toggle=\"yes\">HER2<\/jats:italic>\n                      -mutant cohort had an ORR of 52.9% and a median PFS of 7.5 months (95% CI, 5.4 to not reached).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      iza-bren demonstrated encouraging antitumor activity and a manageable safety profile in pretreated NSCLC patients with diverse GAs outside of classical\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      mutations, especially in\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      exon20ins\/nonclassical and\n                      <jats:italic toggle=\"yes\">HER2<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01929","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T20:59:16Z","timestamp":1772657956000},"page":"893-902","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Izalontamab Brengitecan in Locally Advanced or Metastatic Non\u2013Small Cell Lung Cancer With Actionable Genomic Alterations Outside of Classical\n                    <i>EGFR<\/i>\n                    Mutations: A Phase Ib Study"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3290-1650","authenticated-orcid":true,"given":"Huaqiang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-3888","authenticated-orcid":true,"given":"Hongyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Sun Yat-sen University Cancer Center, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7450-0006","authenticated-orcid":true,"given":"Yongsheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medical Oncology, Fujian Cancer Hospital, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-9449","authenticated-orcid":true,"given":"Yongsheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1173-8441","authenticated-orcid":true,"given":"Yuxiang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Sun Yat-sen University Cancer Center, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7158-3878","authenticated-orcid":true,"given":"Likun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa","family":"Xiao","sequence":"additional","affiliation":[{"name":"Baili\u2014Bio (Chengdu) Pharmaceutical Co, Ltd, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1516-0998","authenticated-orcid":true,"given":"Hai","family":"Zhu","sequence":"additional","affiliation":[{"name":"SystImmune Inc, Washington, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Sichuan Biokin Pharmaceutical Co, Ltd, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-8246","authenticated-orcid":true,"given":"Wenfeng","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-0761","authenticated-orcid":true,"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_12_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_3_12_3_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_3_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30958-8"},{"key":"e_1_3_12_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01626"},{"key":"e_1_3_12_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-1337"},{"key":"e_1_3_12_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0569-6"},{"key":"e_1_3_12_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-022-0976-4"},{"key":"e_1_3_12_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.03.002"},{"key":"e_1_3_12_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00470-8"},{"key":"e_1_3_12_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2112431"},{"key":"e_1_3_12_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01361"},{"key":"e_1_3_12_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03638-2"},{"key":"e_1_3_12_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2025-085680"},{"key":"e_1_3_12_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2025.06.002"},{"key":"e_1_3_12_16_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-24-01349"},{"key":"e_1_3_12_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-24-02744"},{"key":"e_1_3_12_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aao2565"},{"key":"e_1_3_12_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00159-1"},{"key":"e_1_3_12_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-3101"},{"key":"e_1_3_12_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2554"},{"key":"e_1_3_12_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz167"},{"key":"e_1_3_12_23_2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2204.0023"},{"key":"e_1_3_12_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2306441"},{"key":"e_1_3_12_25_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00662"},{"key":"e_1_3_12_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(23)00379-X"},{"key":"e_1_3_12_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2503704"},{"key":"e_1_3_12_28_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.00013"},{"key":"e_1_3_12_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101792"},{"key":"e_1_3_12_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603910"},{"key":"e_1_3_12_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-024-1072-8"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-25-01929","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:59:17Z","timestamp":1774648757000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-25-01929"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,4,1]]}},"alternative-id":["10.1200\/JCO-25-01929"],"URL":"https:\/\/doi.org\/10.1200\/jco-25-01929","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"assertion":[{"value":"2025-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-23","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}