Abstract CT279: DareonTM-5: An open-label phase 2 trial of BI 764532, a DLL3-targeting T-cell engager, in patients (pts) with relapsed/refractory small cell lung cancer or other neuroendocrine carcinomas
Authors: Gambardella Valentina , Greystoke Alastair , Reck Martin , Liu Meiruo , Mueller Martha , Duenzinger Ulrich , Bergsland Emily B. , Owonikoko Taofeek 
Published: April 2024

Abstract
Background: Small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC) of the lung, and extrapulmonary NEC (epNEC) are difficult-to-treat, aggressive tumors with limited treatment options.
Purpose: Many pts relapse and have poor outcomes after standard of care platinum-based chemotherapy ± immunotherapy, underscoring the need for better therapies. BI 764532, a humanized IgG-like T-cell engager, binds to delta-like ligand 3 (DLL3) on the cell surface of these tumors and on CD3 on T cells, consequently promoting T-cell-mediated cytotoxicity. In an ongoing first-in-human trial, BI 764532 exhibited efficacy and manageable tolerability in pts with DLL3-positive SCLC, LCNEC of the lung, and epNEC (NCT04429087). We describe a planned phase 2 dose optimization trial to assess safety/efficacy of 2 different doses of BI 764532 monotherapy in pts with progressive/relapsed SCLC, epNEC, or LCNEC of the lung (NCT05882058).
Experimental design: The trial will recruit adult pts (n=~120; ~70 sites; ~15 countries) with pathologically confirmed relapsed/refractory SCLC, epNEC, or LCNEC of the lung who have received ≥2 (SCLC) or ≥1 (epNEC/LCNEC) prior lines of therapy, including ≥1 platinum-based regimen. Pts with mixed tumor histology are permitted if the SCLC/NEC component is predominant (≥50% of tumor tissue). Pts will be randomized 1:1 to receive 1 of 2 dose levels of IV BI 764532 (3-week cycles) stratified by tumor type (n=~60/arm). Treatment will continue until disease progression, undue toxicity, withdrawal of consent or any other documented criteria for stopping treatment (maximum treatment duration: 36 months). 2 interim dose-selection analyses are planned after 30 pts per dose have been followed for ≥6 and ≥12 weeks or have stopped treatment. A third interim efficacy analysis will be conducted when 60 pts per dose have been followed for ≥12 weeks or have stopped treatment. Key exclusion criteria: Eastern Cooperative Oncology Group performance status ≥2; untreated/symptomatic brain metastases or leptomeningeal disease; active/history of interstitial lung disease/pneumonitis; previous DLL3-targeting treatment; treatment with other anticancer drugs &lt;4 weeks prior to first administration of BI 764532; unresolved toxicity from prior treatment; immunodeficiency diagnosis; intake of immunosuppressive therapy ≤7 days prior to first administration of BI 764532. Primary endpoints: objective response via Response Evaluation Criteria in Solid Tumors v1.1; occurrence of treatment-emergent adverse events (TEAEs). Secondary endpoints: duration of objective response, progression-free survival, disease control, overall survival, patient-reported outcomes, and TEAEs leading to discontinuation. Further endpoints: pharmacokinetics, and prespecified and exploratory biomarker analysis.
Citation Format: Valentina Gambardella, Alastair Greystoke, Martin Reck, Meiruo Liu, Martha Mueller, Ulrich Duenzinger, Emily B. Bergsland, Taofeek Owonikoko. DareonTM-5: An open-label phase 2 trial of BI 764532, a DLL3-targeting T-cell engager, in patients (pts) with relapsed/refractory small cell lung cancer or other neuroendocrine carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT279.