DAREON®-7: Phase I open-label dose-escalation/-expansion study of first-line obrixtamig (BI 764532) plus chemotherapy in patients with DLL3-positive neuroendocrine carcinomas

Aman Chauhan; Saori Mishima,; Ana Custodio,; Timon Vandamme; Patricia Niccoli; Ken Kato; Rocio Garcia-Carbonero; Kazuyoshi Ohkawa; Martin E. Gutierrez; Michael Duruisseaux; Janie Zhang; Julia Koevi; Ping Sun; Michael Woodward; Dian Yang; Jaume Capdevila

doi:10.1530/endoabs.116.C8

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Endocrine Abstracts (2025) 116 C8 | DOI: 10.1530/endoabs.116.C8

NANETS2025 18th Annual Multidisciplinary NET Medical Symposium NANETS 2025 Clinical – Chemo/SSA/Biologics (11 abstracts)

DAREON®-7: Phase I open-label dose-escalation/-expansion study of first-line obrixtamig (BI 764532) plus chemotherapy in patients with DLL3-positive neuroendocrine carcinomas

Aman Chauhan ¹ , Saori Mishima ² , Ana Custodio ³ , Timon Vandamme ^4,5 , Patricia Niccoli ⁶ , Ken Kato ⁷ , Rocio Garcia-Carbonero ⁸ , Kazuyoshi Ohkawa ⁹ , Martin E. Gutierrez ¹⁰ , Michael Duruisseaux ¹¹ , Janie Zhang ¹² , Julia Koevi ¹³ , Ping Sun ¹⁴ , Michael Woodward ¹⁵ , Dian Yang ¹⁶ & Jaume Capdevila ¹⁷

Author affiliations

¹Department of Internal Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; ²Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; ³Medical Oncology Department, Hospital Universitario La Paz, Instituto de Investigación Biomédica Hospital Universitario La Paz (IdiPAZ), Madrid, Spain; ⁴Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp; ⁵NETwerk & Department of Oncology, Antwerp University Hospital, Antwerp, Belgium; ⁶Institut Paoli Calmettes, Department of Oncology, Marseille, France; ⁷Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; ⁸Medical Oncology Department, Hospital Universitario 12 de Octubre, Medicine Faculty, Universidad Complutense de Madrid, Spain; ⁹Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan; ¹⁰Hackensack University Medical Center at Hackensack Meridian Health, Hackensack, NJ, USA; ¹¹Louis Pradel Hospital, Hospices Civils de Lyon Cancer Institute, Lyon, France; ¹²Department of Internal Medicine, Division of Malignant Hematology and Medical Oncology, University of Pittsburgh School of Medicine and Hillman Cancer Center, Pittsburgh, PA, USA; ¹³Boehringer Ingelheim International GmbH, Biberach an der Riss, Germany; ¹⁴Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA;¹⁵Syneos Health by delegation of Boehringer Ingelheim Spain, S.A. Sant Cugat;¹⁶Department of Oncology, Boehringer Ingelheim (China) Investment Co., Ltd., Shanghai, China; ¹⁷Department of Medical Oncology, Vall d’Hebron University Hospital & Vall d’Hebron Institute of Oncology, Barcelona, Spain

Background: Delta-like ligand 3 (DLL3) is widely expressed in neuroendocrine carcinomas (NECs). Obrixtamig is a DLL3/CD3 IgG-like T-cell engager that binds simultaneously to DLL3 on tumor cells and CD3 on T-cells. We report initial safety and efficacy data from the dose escalation part of the Phase I DAREON®-7 (NCT06132113) trial assessing obrixtamig plus simultaneous chemotherapy (carboplatin plus etoposide) in patients with DLL3-positive NECs.

Methods: Patients had locally advanced/metastatic DLL3-positive extrapulmonary NEC (epNEC), large cell NEC of the lung (LCNEC-L), or NEC of unknown primary site. Obrixtamig was given as step-up dosing followed by target dose (3 dose levels), guided by a Bayesian Logistic Regression Model with overdose control. Carboplatin plus etoposide was given per label. Antitumor activity was assessed using RECIST v1.1 (investigator-assessed). The ongoing dose expansion part will assess obrixtamig plus chemotherapy at the dose selected during dose escalation.

Results: As of May 16, 2025, 27 patients were enrolled (epNEC: 78%, LCNEC-L: 7%, unknown primary site: 15%; median age: 67 years (range: 42–79); ECOG PS:0/1, 70%/30%). Overall, 26 patients received ≥1 dose of obrixtamig plus carboplatin and etoposide; in these patients, median number of obrixtamig cycles: 7 (range: 1–14); median treatment exposure: 4.4 months (range: 0.1–8.9). There were no dose-limiting toxicities; maximum tolerated dose was not reached. Most frequent adverse events (AEs) are shown in Table 1. No patients discontinued obrixtamig due to AEs. One patient (4%) experienced a potential obrixtamig-related neurotoxicity (grade [G]1 immune effector cell-associated neurotoxicity syndrome). One patient (4%) experienced G3 febrile neutropenia. Among 16 patients with cytokine release syndrome (CRS; 59%), most cases (n = 13, 48%) were G1, with no cases G≥3. Confirmed objective response rate in evaluable patients (n = 21): 76% (95% CI: 55–89; partial response 76%, stable disease 10%, progressive disease 10%); disease control rate: 86% (95% CI: 65–95). Confirmed median duration of response was not reached.


Most common AEs
n (%)
AEs (in n≥10)	25 (93)	21 (78)
Neutropenia and/or neutrophil count decreased	17 (63)	16 (59)
CRS	16 (59)	0
Constipation	13 (48)	0
Anemia	12 (44)	9 (33)
Decreased appetite	10 (37)	1 (4)
Dysgeusia	10 (37)	0
Obrixtamig-related AEs	23 (85)	1 (4)

Conclusions: Obrixtamig plus chemotherapy was tolerable with no unexpected toxicities. The reported frequency/severity of AEs was consistent with the expected safety profile of the individual treatments, with no additional toxicities. Preliminary efficacy results were encouraging, warranting further development of the combination in this setting.

Abstract ID #33390