686TiP - Preliminary phase I results from a first-in-human study of ZG006, a trispecific anti-T cell engager targeting CD3/DLL3/DLL3, as monotherapy in patients with advanced small cell lung cancer or neuroendocrine carcinoma

Background

ZG006 is a trispecific anti-T cell engager (Tri-TE) targeting Delta-like ligand 3 (DLL3) and CD3, designed to bridge tumor cells and T cells by binding to two distinct DLL3 epitopes on tumor cells and CD3 on T cells, thereby mediating tumor-infiltrating T cell-specific killing of DLL3-expressing tumor cells such as small cell lung cancer and neuroendocrine carcinomas. Based on its molecular structure, ZG006 may have excellent cytotoxic effects against tumors with low DLL3 expression. Preclinical pharmacological and toxicological studies have demonstrated that ZG006 exhibits promising anti-tumor activity and favorable safety profiles both in vitro and in vivo. We have conducted a Phase I clinical study to assess the tolerability, safety, preliminary efficacy of ZG006.

Trial design

This is a multi-center, open-label, Phase I clinical study of ZG006 for the treatment of subjects with advanced small cell lung cancer or neuroendocrine carcinoma who had no standard treatment available, or were intolerant to standard treatment. During the dose escalation stage, an accelerated titration design (ATD) combined with the standard “3+3” design will be used to assess the Recommended Phase 2 Dose (RP2D) for the subsequent studies. Therefore, the dose groups of ZG006 for dose escalations are set as 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg and 30 mg, intravenous administration, once every two weeks. The first 28-day-period was defined as the dose-limiting toxicity (DLT) observation period. After the completion of the DLT observation period, subjects can continue to receive ZG006 treatment until the occurrence of intolerable toxicity, disease progression, initiation of new anti-tumor therapy, withdrawal of consent (whichever comes first). Imaging efficacy assessments are conducted every 6 weeks within 48 weeks post-initial dosing, followed by assessments every 12 weeks thereafter. Tumor response was assessed by RECIST1.1. Pharmacokinetics and DLL3 expressions were also assessed in this study.

Clinical trial identification

NCT05978284.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Suzhou Zelgen BioPharmaceuticals. Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.