ZL-1310 (DLL3-targeted topo-I ADC) drives 48% ORR in platinum-refractory extrapulmonary NEC (early Phase 1b)

ZL-1310 is a DLL3-targeted antibody–drug conjugate delivering a topoisomerase I inhibitor payload via a protease-cleavable linker (TMALIN® platform). In the Phase 1b/2 ZL-1310-002 study (NCT06885281), patients with advanced/metastatic de novo neuroendocrine carcinomas excluding SCLC who had progressed on/after platinum chemotherapy received ZL-1310 1.6mg/kg IV Q3W (n=28; 21 evaluable; DLL3 IHC positive in 80% [21/26], H-score cutoff ≥1) with short median follow-up of 2.9 months. ORR was 48% (8 confirmed + 2 unconfirmed responses/21), which is well above typical second-line chemotherapy benchmarks in extrapulmonary NEC (e.g., randomized Phase 2 SENECA showed ORR ~28% with CAPTEM or FOLFIRI; older retrospective FOLFIRI series report ORR ~20–30% with median PFS ~3 months), while early safety looked manageable (Grade 3+ TEAEs 14.3%; common TEAEs anemia 39%, nausea 36%, vomiting 29%; 1 dose reduction [3.6%] and 1 discontinuation for Grade 2 ILD [3.6%]; no Grade 5 events).