CTIM-30 - A Phase 1b, open-label, dose-escalation trial of the delta-like ligand 3 (DLL3)/CD3 IgG-like T cell engager, BI 764532, in patients with DLL3-positive glioma

Friday, November 17, 2023

7:30 PM – 9:30 PM PT

Location: Exhibit Hall A/B

Poster Presenter(s)

Martin J. van den Bent

Erasmus MC Cancer Institute
Rotterdam, Netherlands

Author(s)

Patrick Roth

Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
Zurich, Zurich, Switzerland
Ghazaleh Tabatabai

University Hospital Tübingen and Eberhard Karls University Tübingen
Tübingen, Baden-Wurttemberg, Germany
MB

Michael C. Burger

Dr Senckenberg Institute of Neurooncology, Goethe University Hospital
Frankfurt, Germany
MM

Maria Martinez-Garcia

Department of Medical Oncology, Hospital del Mar-CIBERONC
Barcelona, Spain
Louisa von Baumgarten

Dept. of Neurosurgery, Ludwig Maximilians University (LMU) Munich,
Munich, Bayern, Germany
RG

Richard Greil

IIIrd Medical Department, Paracelsus Medical University Salzburg; Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials (SCRI-CCCIT); Cancer Cluster Salzburg
Salzburg, Austria
MS

Matus Studeny

Boehringer Ingelheim International GmbH
Ingelheim, Germany
MS

Monika Simetzberger

Boehringer Ingelheim RCV GmbH & Co KG
Vienna, Austria
ML

Meiruo Liu

Boehringer Ingelheim (China) Investment Co. Ltd, Biostatistics and Data Sciences
Shanghai, China (People's Republic)

Background: Patients with progressive diffuse gliomas have limited treatment options. DLL3, a Notch ligand, is expressed on most diffuse gliomas. BI 764532, a humanized IgG-like T cell engager, binds selectively to DLL3-positive cells and promotes T cell-mediated cytotoxicity. Preclinical data showed activity of BI 764532 against intracranial tumors. In an ongoing first-in-human trial in patients with DLL3-positive small-cell lung carcinoma and other neuroendocrine carcinomas (NECs) including extrapulmonary NECs and large-cell NECs of the lung (NCT04429087), BI 764532 exhibited promising efficacy and manageable tolerability. Here we describe a planned Phase Ib dose-escalation/expansion trial of BI 764532 monotherapy in patients with DLL3-positive refractory/relapsed diffuse glioma.

Methods: The dose-escalation part will include ~12─20 patients (≥3 patients per dose level) from 12 sites across Europe/USA. Dose escalation will be guided by Bayesian logistic regression model with overdose control. BI 764532 will be administered intravenously. Treatment will continue until disease progression, undue toxicity, informed consent withdrawn, or other reasons requiring treatment discontinuation. Once a recommended dose for expansion is established, ~15 patients from Europe will be treated in a dose-expansion phase. Key inclusion criteria: ≥18 years old; histologically confirmed primary progressive diffuse glioma who have failed on standard-of-care therapies; DLL3-positivity by IHC on archived tumor tissue by central pathology review. Key exclusion criteria: extracranial metastatic or leptomeningeal disease; previous treatment with DLL3-targeting therapies; prior treatment with bevacizumab/other anti-VEGF/anti-angiogenic treatment ≤6 months prior to first administration of BI 764532; persistent toxicity from previous treatments that has not resolved to ≤CTCAE Grade 1; diagnosis of immunodeficiency, or intake of immunosuppressive therapy ≤7 days prior to first administration of BI 764532. Primary endpoints: dose-limiting toxicities (DLTs) during the maximum tolerated dose evaluation period (escalation phase); DLTs during the entire treatment period (expansion phase). Other objectives include pharmacokinetics, pharmacodynamics, preliminary efficacy and evaluation of DLL3 as a potential biomarker.