ZL-1310 (Zocilurtatug Pelitecan): A Novel DLL3-Targeted Antibody-Drug Conjugate Leveraging the TMALIN® Platform for the Treatment of Small Cell Lung Cancer and Other Solid Tumors – A Comprehensive Clinical and Regulatory Review

1. Executive Summary

ZL-1310, also known by its proposed non-proprietary name zocilurtatug pelitecan, is an investigational first-in-class antibody-drug conjugate (ADC) targeting Delta-like ligand 3 (DLL3).[1] This therapeutic agent utilizes the proprietary TMALIN® (Tumor Microenvironment Activable LINker-payload) platform technology developed by MediLink Therapeutics and is currently under global development by Zai Lab.[3] ZL-1310 is being evaluated for its potential to address the significant unmet medical need in extensive-stage small cell lung cancer (ES-SCLC), an aggressive malignancy with a historically poor prognosis, and it holds promise for other DLL3-expressing neuroendocrine tumors.[1]

The ongoing global Phase 1a/1b clinical trial (NCT06179069) has yielded encouraging results, particularly highlighted at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. In heavily pretreated ES-SCLC patients, ZL-1310 demonstrated clinically meaningful anti-tumor activity. Specifically, in the second-line (2L) SCLC setting, an objective response rate (ORR) of 67% was observed across all dose levels (n=33), which increased to an impressive 79% at the 1.6 mg/kg dose level (n=14). Notably, clinical activity was also observed in patients with brain metastases and across various levels of DLL3 expression. The safety profile of ZL-1310, especially at doses below 2.0 mg/kg (where Grade ≥3 treatment-related adverse events, or TRAEs, occurred in 6% of patients), appears manageable. Key adverse events requiring careful monitoring include hematological toxicities and interstitial lung disease (ILD).[1]