Obrixtamig (BI 764532) in patients with relapsed/refractory delta-like ligand 3 (DLL3) high-expressing extrapulmonary neuroendocrine carcinoma (epNEC): trial in progress of the dose expansion part of the Phase II DAREON-5 trial
Presenter: Andrea Standring Session: Phase II and Phase III Clinical Trials in Progress Time: 4/21/2026 9:00:00 AM → 4/21/2026 12:00:00 PM
Authors
Marianne Pavel 1 , Chris Verslype 2 , Pedro Rocha 3 , Alastair Greystoke 4 , Aman Chauhan 5 , Julia Koevi 6 , Martha Mueller 7 , Eric Song 8 , Valeria Lifke 9 , Andrea Standring 10 , Emily Bergsland 11 1 Department of Medicine 1, Friedrich-Alexander-University of Erlangen-Nürnberg, Ulmenweg 18, Erlangen, Germany, 2 Department of Gastroenterology and Hepatology, University Hospitals Leuven, Erlangen, Germany, 3 Medical Oncology Department, Valld’Hebron University Hospital, Barcelona, Spain, 4 Translational and Clinical Research Institute, NU Cancer, Newcastle University, Newcastle upon Tyne, United Kingdom, 5 Department of Internal Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 6 TA Oncology Medicine, Boehringer Ingelheim International GmbH, Biberach an der Riss, Germany, 7 Global Clinical Development & Operations, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, 8 Biostatistics & Data Sciences, Boehringer Ingelheim (China) Investment Co., Ltd., Shanghai, China, 9 Global Exploratory Medicine Oncology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, 10 Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, 11 Department of Medicine, University of California, San Francisco (UCSF), San Francisco, CA
Abstract
Background: Patients with relapsed/refractory extrapulmonary neuroendocrine carcinoma (epNEC) have poor outcomes with currently available therapies. Delta-like ligand 3 (DLL3) is expressed on the surface of many epNEC cells, offering a promising therapeutic target. Obrixtamig (BI 764532) is a DLL3/CD3 IgG-like T-cell engager that binds simultaneously to CD3 on T-cells and DLL3 on tumor cells, resulting in immune-mediated tumor cell lysis. In an ongoing first-in-human Phase I trial, obrixtamig monotherapy had promising efficacy in patients with DLL3+ small cell lung cancer (SCLC), epNEC, or large cell NEC of the lung (LCNEC-L) and a manageable toxicity profile, justifying further clinical investigation. The Phase II DAREON-5 trial is a dose-selection and -expansion trial of obrixtamig monotherapy in patients with histologically confirmed relapsed/refractory SCLC, epNEC, or LCNEC-L after prior standard of care therapy. The completed dose-selection part evaluated the safety and efficacy of 2 obrixtamig doses. We describe the design of the expansion part of the study that is currently enrolling. Methods: The expansion part of DAREON-5 is assessing obrixtamig antitumor activity at the selected dose for expansion in patients with centrally assessed DLL3 high-expressing epNEC (NCT05882058); defined as ≥50% of evaluable tumor cells with moderate to strong membrane and/or cytoplasmic DLL3 staining using the VENTANA DLL3 (SP347) assay. Eligible patients have relapsed/refractory, advanced/metastatic, histologically confirmed epNEC after prior platinum-based chemotherapy (≥1 line of therapy). Patients will receive intravenous obrixtamig infusions as step-up doses followed by the target dose. Primary endpoint is objective response per Response Evaluation Criteria in Solid Tumors version 1.1, assessed by blinded independent central review. Secondary endpoints include duration of objective response, progression-free survival, disease control, overall survival, treatment-emergent adverse events, and patient-reported outcomes. The planned enrollment for the expansion cohort is ~50 patients recruited from the following countries: Belgium, China, Germany, Japan, Portugal, South Korea, Spain, UK, and USA.
Disclosure
M. Pavel, AAA Independent Contractor, ), Other, Steering Committee Member. Esteve Pharma Limited Independent Contractor. ITM Independent Contractor, ). SERB Independent Contractor. Tairix Independent Contractor. Netzwerk NET Independent Contractor. IPSEN Independent Contractor. Boehringer IngeIheim, Inc. Independent Contractor, ). Eli Lilly Independent Contractor. MSD Independent Contractor. Novartis Independent Contractor, ), Other, Steering Committee Member. Recordati Independent Contractor. Sanofi Independent Contractor. Crinetics Other, Steering Committee Member. C. Verslype, IPSEN Independent Contractor. AstraZeneca Independent Contractor. Bayer Independent Contractor. P. Rocha, AstraZeneca Travel. MSD Travel. BMS Travel. Kiowa Kirin Travel. Amgen Independent Contractor. Daiichi Sankyo Independent Contractor. IGES Independent Contractor. A. Greystoke, Foundation Medicine Independent Contractor. Guardant Independent Contractor. AstraZeneca Independent Contractor, ). Janssen Independent Contractor, Travel. Pfizer Independent Contractor. Lilly Independent Contractor. Boehringer Ingelheim Independent Contractor. MSD Independent Contractor. Takeda Independent Contractor, Travel. BMSi Independent Contractor. Novartis Independent Contractor. Roche Independent Contractor, Travel. Sanofi Independent Contractor. Merck Independent Contractor. Amgen Independent Contractor. A. Chauhan, Boehringer Ingelheim Independent Contractor. Crinetics Independent Contractor. Curium Independent Contractor. Exelixis Independent Contractor. Novartis Independent Contractor. Bristol Myers Squibb ). Clovis Oncology ). Merck ). Nano Therapeutics ). TerSera Independent Contractor, ). Elicio Therapeutics Stock. Revolution Medicine Stock. Entrinsic Health Solutions Travel. J. Koevi, Boehringer Ingelheim Inc. Employment. M. Mueller, Boehringer Ingelheim Inc. Employment. E. Song, Boehringer Ingelheim Inc. Employment. V. Lifke, Boehringer Ingelheim Inc. Employment. A. Standring, Boehringer Ingelheim, Inc. Employment. E. Bergsland, Boehringer Ingelheim, Inc. ). Merck ). RayzeBio ). More Health g., Board of Directors, non-salaried role), Stock. Exai Bio g., Board of Directors, non-salaried role).
Cited in
Control: 11036 · Presentation Id: 12242 · Meeting 21436