{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:59:32Z","timestamp":1793282372357,"version":"4.5.0"},"reference-count":39,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"27","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,9,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>We report phase I results for obrixtamig (BI 764532), a delta-like ligand 3 (DLL3)\/CD3 IgG-like T-cell engager, in patients with previously treated DLL3-positive small cell lung cancer (SCLC), extrapulmonary neuroendocrine carcinomas (epNECs), or large cell neuroendocrine carcinoma of the lung (LCNEC-L).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients received escalating intravenous obrixtamig doses using four regimens: a fixed dose once every 3 weeks (A); a fixed dose once weekly (B1); a step-up dose once weekly for two weeks and target dose once weekly (B2); and a step-up dose once weekly for 3 weeks, target dose once weekly for 3 weeks, and once every 3 weeks thereafter (B3). The primary objective was maximum tolerated dose (MTD). Secondary objectives included safety, pharmacokinetics, and tumor response (RECIST v1.1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>As of February 21, 2024, 168 patients received obrixtamig, 72% received \u22652 lines of previous anticancer therapy, and 51% received previous anti\u2013PD-1\/PD-L1 therapy. Seven dose-limiting toxicities occurred during MTD evaluation (Regimen A, n = 1; Regimen B2, n = 6). MTD was not reached. The most common treatment-related adverse event was cytokine release syndrome (any grade: 57%; grade \u22653: 3%); most cases occurred early and were reversible. Across all doses, regimens, and tumor types, the overall response rate (ORR) was 23% (95% CI, 17.4% to 30.2%), the median duration of response (DoR) was 8.5 months (95% CI, 6.2 to not reached), and the 6-month DoR rate was 70% (95% CI, 53% to 88%). All patients in Regimens B2\/B3 received the minimum effective dose (\u226590 \u03bcg\/kg once weekly or once every 3 weeks), achieving an ORR of 28% (95% CI, 20.7% to 35.9%). With Regimens B2\/B3, ORRs were 21% (95% CI, 12.9% to 33.1%), 27% (95% CI, 17.4% to 39.6%), and 70% (95% CI, 39.7% to 89.2%) for SCLC, epNECs, and LCNEC-L, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The demonstrated tolerability and efficacy of obrixtamig regimens, administered as step-up followed by target doses of 90-1,080 \u03bcg\/kg (once weekly or once every 3 weeks), in patients with heavily pretreated DLL3-positive tumors support further exploration in SCLC, epNEC, and LCNEC-L.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00363","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T19:59:33Z","timestamp":1753387173000},"page":"3021-3031","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":52,"title":["Phase I Dose-Escalation Results for the Delta-Like Ligand 3\/CD3 IgG-Like T-Cell Engager Obrixtamig (BI 764532) in Patients With Delta-Like Ligand 3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04429087","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4844-4087","authenticated-orcid":true,"given":"Martin","family":"Wermke","sequence":"first","affiliation":[{"name":"TU Dresden University of Technology, NCT\/UCC Early Clinical Trial Unit, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6081-8830","authenticated-orcid":true,"given":"Valentina","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednico Universitario, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3675-953X","authenticated-orcid":true,"given":"Yasutoshi","family":"Kuboki","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-0098","authenticated-orcid":true,"given":"Enriqueta","family":"Felip","sequence":"additional","affiliation":[{"name":"Department of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel F.","family":"Sanmamed","sequence":"additional","affiliation":[{"name":"Department of Oncology, Cl\u00ednica Universidad de Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8079-4725","authenticated-orcid":true,"given":"Olatunji B.","family":"Alese","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus M.","family":"Sayehli","sequence":"additional","affiliation":[{"name":"Interdisciplinary Study Center with ECTU, Medical Clinic and Polyclinic II of the University Hospital, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8960-7519","authenticated-orcid":true,"given":"Edurne","family":"Arriola","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital del Mar-CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Oncolog\u00eda), Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions M\u00e8diques), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8833-8812","authenticated-orcid":true,"given":"J\u00fcrgen","family":"Wolf","sequence":"additional","affiliation":[{"name":"Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-523X","authenticated-orcid":true,"given":"Liza C.","family":"Villaruz","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Bertulis","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. 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