ZL-1310 (DLL3-targeted topo I ADC) drives 58% intracranial responses in ES-SCLC brain mets

ZL-1310 is a DLL3-targeted antibody–drug conjugate using the TMALIN® platform (protease-cleavable linker delivering a topoisomerase I inhibitor payload) evaluated in a multi-country Phase 1 dose-escalation trial in previously treated ES-SCLC after ≥1 platinum regimen (NCT06179069). Among patients with baseline brain metastases with independent intracranial (mRANO) readouts available (n=24; 9 untreated BM, 15 post-radiation), confirmed intracranial ORR was 58.3% (14/24; 5 CR, 9 PR) with intracranial DCR 95.8% and median time to intracranial response 5.6 weeks; intracranial ORR was 66.7% (6/9) without prior brain radiation vs 53.3% (8/15) with prior radiation. Systemically in the BM subset with evaluable disease (n=33), confirmed ORR was 61% (1 CR); grade ≥3 TRAEs were 21.2% overall (22/104) and 12.8% at 1.6 mg/kg (5/39), with anemia and neutropenia the only grade ≥3 TRAEs occurring in ≥2 patients at 1.6 mg/kg—benchmarking against common 2L options like lurbinectedin (~35% ORR in its registrational Phase 2) and topotecan (often ~7–10% ORR in relapsed/refractory disease), these response rates look well above typical cytotoxic salvage ranges, though cross-trial comparisons and small intracranial n apply.