{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T20:22:41Z","timestamp":1784924561721,"version":"3.55.0"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"abstract":"\n PURPOSE<\/jats:title>\n Small cell lung cancer (SCLC) remains one of the most aggressive malignancies, with limited treatment options beyond frontline chemo-immunotherapy. Izalontamab brengitecan (iza-bren, BL-B01D1) is a first-in-class bispecific antibody-drug conjugate cotargeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3). We expanded the SCLC cohort to further evaluate the efficacy and safety of iza-bren in patients with extensive-stage SCLC (ES-SCLC).<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n This open-label, multicenter, dose-expansion phase Ib study (ClinicalTrials.gov identifier:\n NCT05194982<\/jats:ext-link>\n ) enrolled patients with ES-SCLC who had progressed on prior systemic therapies. Patients received iza-bren 2.5 mg\/kg once daily on days 1 and 8 of each 3-week cycle. The primary end points were objective response rate (ORR) and safety\/tolerability. Secondary end points included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory end point included the assessment of potential associations between EGFR\/HER3 expression and clinical outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n As of December 5, 2024, 52 patients were enrolled. The ORR was 48.1% (95% CI, 34.0 to 62.4), with a median PFS of 4.1 months (95% CI, 3.0 to 5.5) and a median OS of 12.2 months (95% CI, 9.1 to 13.2). In patients who received iza-bren as second-line treatment (n = 22), the ORR was 72.7% (95% CI, 49.8 to 89.3), median PFS 6.2 months (95% CI, 3.7 to 8.2), and median OS 15.0 months (95% CI, 8.7 to not reached). The most common treatment-related adverse events were hematologic toxicities (neutropenia, thrombocytopenia, anemia, and leukopenia). Exploratory biomarker analysis suggested that positive HER3 expression may be associated with better treatment response.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n Iza-bren showed encouraging antitumor activity in relapsed ES-SCLC, particularly in the second-line setting. A phase III randomized controlled trial of iza-bren compared with topotecan (ClinicalTrials.gov identifier:\n NCT06500026<\/jats:ext-link>\n ) is ongoing.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/jco-26-00243","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T20:00:16Z","timestamp":1784923216000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Izalontamab Brengitecan (Iza-Bren), a First-in-Class EGFR-HER3 Bispecific Antibody-Drug Conjugate in Extensive-Stage Small Cell Lung Cancer: Results From a Phase Ib Study"],"prefix":"10.1200","clinical-trial-number":[{"clinical-trial-number":"nct05194982","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Yuanyuan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-3888","authenticated-orcid":false,"given":"Hongyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7813-2885","authenticated-orcid":false,"given":"Qiming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-4736","authenticated-orcid":false,"given":"Kunyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-9449","authenticated-orcid":false,"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\/0000-0003-2416-9591","authenticated-orcid":false,"given":"Zhenming","family":"Fu","sequence":"additional","affiliation":[{"name":"Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory, Shanxi Tumor Hospital, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, National Health Commission (NHC) Key Laboratory of Cancer Metabolism, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biotherapy and Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1173-8441","authenticated-orcid":false,"given":"Yuxiang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, 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, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-8246","authenticated-orcid":false,"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, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa","family":"Xiao","sequence":"additional","affiliation":[{"name":"Baili-Bio (Chengdu) Pharmaceutical, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1516-0998","authenticated-orcid":false,"given":"Hai","family":"Zhu","sequence":"additional","affiliation":[{"name":"SystImmune, Redmond, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Sichuan Biokin Pharmaceutical, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-0761","authenticated-orcid":false,"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, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1789-5088","authenticated-orcid":false,"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, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"e_1_3_12_2_2","unstructured":"Surveillance E and End Results: Small cell carcinoma of the lung and bronchus. 2024. https:\/\/seer.cancer.gov\/statistics"},{"key":"e_1_3_12_3_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21785"},{"key":"e_1_3_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2024.107924"},{"key":"e_1_3_12_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.0560"},{"key":"e_1_3_12_6_2","article-title":"Antibody-drug conjugates in SCLC: DLL3, B7-H3, TROP2, and beyond","author":"Monaca F","unstructured":"Monaca F, Gomez-Randulfe I, Torres-Jim\u00e9nez J, et al: Antibody-drug conjugates in SCLC: DLL3, B7-H3, TROP2, and beyond. 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