DAREON™-7: A Phase I, open-label, dose escalation and expansion cohort trial of the delta-like ligand (DLL3)-targeting T-cell engager BI 764532, plus first-line platinum-based chemotherapy in patients with DLL3-positive neuroendocrine carcinomas

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Introduction: Neuroendocrine carcinomas (NEC) have limited treatment options. DLL3 is highly expressed on NEC and is a promising treatment target. In an ongoing Phase I trial (NCT04429087), BI 764532, a DLL3/CD3 IgG-like T-cell engager (TcE), was tolerable with promising activity in pretreated pts with DLL3-positive (+) tumours, including NEC.

Aim(s): DAREON™-7, a Phase I, open-label, dose escalation (Part A) and expansion (Part B) trial, aims to determine the maximum tolerated dose (MTD), recommended dose for expansion (RDE) / recommended Phase II dose (RP2D), safety and efficacy of BI 764532 + platinum and etoposide in pts with DLL3+ NEC.

Materials and methods: Part A: ~25 pts will receive IV BI 764532 (target dose after step-in dosing) plus carboplatin/etoposide (CE) until RECIST 1.1 progression, intolerable toxicity, or for a maximum of 36 months. Escalation of BI 764532 dose will be guided by a Bayesian Logistic Regression Model with overdose control. Part B: two cohorts (~15 pts each) will receive BI 764532 at the RDE/RP2D + CE or cisplatin/etoposide (as most used standard of care regimens). Key inclusion criteria: first-line treatment for confirmed DLL3+ locally advanced/metastatic NEC (extra pulmonary or unknown primary) or large cell NEC of the lung; prior adjuvant therapy allowed if >6 months. Pts are adequate candidates to receive etoposide + platinum as the standard of care treatment. Primary endpoints: occurrence of dose-limiting toxicities (DLTs) in the MTD evaluation (Part A) and on-treatment (Part B) periods. Secondary endpoints: occurrence of DLTs and adverse events during the on-treatment period (Part B) and efficacy measured by objective response and duration of response (Part B). Enrolment is ongoing.

Conference:

Presenting Author: Capdevila J

Authors: Capdevila J, Vandamme T, Niccoli P, Mishima S, Kato K,

Keywords: neuroendocrine carcinoma, delta-like ligand, T-cell engager, Phase I,