PO.CTP01.03 · 进行中的临床试验

Obrixtamig（BI 764532）用于复发/难治性delta样配体3（DLL3）高表达的肺外神经内分泌癌（epNEC）患者：II期DAREON-5试验剂量扩展部分的进行中试验

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

编号 CT222 展板 17 时间 4/21 09:00–12:00 区域 Section 51 主讲 Andrea Standring

分会场 Phase II and Phase III Clinical Trials in Progress

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作者与单位 Authors & Affiliations

Marianne Pavel¹, Chris Verslype², Pedro Rocha³, Alastair Greystoke⁴, Aman Chauhan⁵, Julia Koevi⁶, Martha Mueller⁷, Eric Song⁸, Valeria Lifke⁹, Andrea Standring¹⁰, Emily Bergsland¹¹

¹Department of Medicine 1, Friedrich-Alexander-University of Erlangen-Nürnberg, Ulmenweg 18, Erlangen, Germany,²Department of Gastroenterology and Hepatology, University Hospitals Leuven, Erlangen, Germany,³Medical Oncology Department, Valld’Hebron University Hospital, Barcelona, Spain,⁴Translational and Clinical Research Institute, NU Cancer, Newcastle University, Newcastle upon Tyne, United Kingdom,⁵Department of Internal Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL,⁶TA Oncology Medicine, Boehringer Ingelheim International GmbH, Biberach an der Riss, Germany,⁷Global Clinical Development & Operations, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany,⁸Biostatistics & Data Sciences, Boehringer Ingelheim (China) Investment Co., Ltd., Shanghai, China,⁹Global Exploratory Medicine Oncology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany,¹⁰Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT,¹¹Department of Medicine, University of California, San Francisco (UCSF), San Francisco, CA

摘要 Abstract

中文摘要

背景：复发/难治性肺外神经内分泌癌（epNEC）患者使用现有疗法的结局较差。Delta样配体3（DLL3）表达于许多epNEC细胞表面，提供了一个有前景的治疗靶点。Obrixtamig（BI 764532）是一种DLL3/CD3 IgG样T细胞衔接器，可同时与T细胞上的CD3和肿瘤细胞上的DLL3结合，从而导致免疫介导的肿瘤细胞裂解。在一项正在进行的首次人体I期试验中，obrixtamig单药治疗在DLL3+小细胞肺癌（SCLC）、epNEC或肺大细胞神经内分泌癌（LCNEC-L）患者中显示出有前景的疗效和可管理的毒性特征，为进一步临床研究提供了依据。II期DAREON-5试验是一项obrixtamig单药治疗的剂量选择和剂量扩展试验，用于经组织学确诊、既往接受标准治疗后复发/难治性的SCLC、epNEC或LCNEC-L患者。已完成的剂量选择部分评估了2种obrixtamig剂量的安全性和疗效。我们描述该研究目前正在入组的扩展部分的设计。方法：DAREON-5的扩展部分正在评估obrixtamig在所选扩展剂量下对中心评估的DLL3高表达epNEC患者的抗肿瘤活性（NCT05882058）；DLL3高表达定义为使用VENTANA DLL3（SP347）检测，≥50%的可评估肿瘤细胞出现中至强的膜和/或细胞质DLL3染色。合格患者为既往接受铂类化疗后（≥1线治疗）、复发/难治性、晚期/转移性、组织学确诊的epNEC。患者将接受静脉输注obrixtamig，采用递增剂量后给予目标剂量。主要终点是根据实体瘤疗效评价标准1.1版、由盲态独立中心审查评估的客观缓解。次要终点包括客观缓解持续时间、无进展生存、疾病控制、总生存、治疗中出现的不良事件和患者报告结局。扩展队列计划入组约50例患者，招募自以下国家：比利时、中国、德国、日本、葡萄牙、韩国、西班牙、英国和美国。

查看英文原文 English 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.

利益披露 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).

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