ZG006, a trispecific T-cell engager targeting delta-like ligand 3 (DLL3) and CD3, is designed to mediate T cell–specific killing of DLL3-expressing tumor cells, such as small cell lung cancer (SCLC). This phase 2 dose-expansion study evaluated ZG006 monotherapy in patients with advanced SCLC who had failed at least 2 prior lines of systemic therapy.
Patients were randomized 1:1 to receive ZG006 10 mg intravenously (IV) every 2 weeks (N=30) or ZG006 30 mg IV every 2 weeks (N=30). The primary endpoint was objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), duration of response (DOR), overall survival, and safety.
Out of the 24 patients evaluable for efficacy in both the 10-mg and 30-mg group, no patients had a complete response, while 62.5% and 58.3% of patients had a partial response, respectively. In the 10-mg group, the ORR was 62.5% and the disease control rate (DCR) was 70.8%, while in the 30-mg group, the ORR was 58.3% and the DCR was 66.7%.
Treatment-related adverse events (TRAEs) were reported in 100% of patients, with the most common being pyrexia (10 mg, 79.2%; 30 mg, 79.2%), cytokine release syndrome (CRS) (10 mg, 41.7%; 30 mg, 75.0%), vomiting (10 mg, 16.7%; 30 mg, 41.7%), and rash (10 mg, 16.7%; 30 mg, 25.0%). Within the 10-mg and 30-mg group, 29.2% and 45.8% of patients experienced grade ≥3 TRAEs, respectively, with 2 patients experiencing grade ≥3 CRS in the 30-mg group. One TRAE in the 30-mg group led to treatment discontinuation or death. Safety profiles were similar across the 10-mg and 30-mg dose groups.
ZG006 demonstrated promising efficacy and an acceptable safety profile among patients with SCLC who were heavily pretreated. The ongoing phase 2 study continues to explore its potential as a novel therapeutic option for advanced SCLC.
Source: Ai S, et al. A phase 2 dose expansion study of ZG006, a trispecific T cell engager targeting CD3/DLL3/DLL3, as monotherapy in patients with advanced small cell lung cancer. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 8007.