ZL-1310

Overview

ZL-1310 (zocilurtatug pelitecan) is an investigational, DLL3‑targeted antibody–drug conjugate (ADC) being developed by Zai Lab for DLL3‑expressing solid tumors, with the lead indication in extensive‑stage small cell lung cancer (ES‑SCLC). In 2025, the FDA granted both Orphan Drug designation (January 22, 2025) and Fast Track designation (May 19, 2025) for ES‑SCLC. A randomized pivotal study in second‑line (2L) ES‑SCLC is planned following Phase 1a/1b results presented at ASCO 2025. (ir.zailaboratory.com)

Mechanism of action

• Target: Delta‑like ligand 3 (DLL3), aberrantly expressed on the surface of most SCLC and other high‑grade neuroendocrine carcinomas, with limited normal‑tissue expression. (ascopubs.org)
• Modality: ADC composed of a humanized anti‑DLL3 monoclonal antibody conjugated via a tumor‑microenvironment–activatable linker (TMALIN platform) to a camptothecin‑derived topoisomerase‑1 inhibitor payload (reported drug‑to‑antibody ratio ≈8 in preclinical work). (oncologypro.esmo.org)

Preclinical studies showed potent, DLL3‑specific binding and internalization, induction of apoptosis, tumor growth inhibition in DLL3+ xenografts, and favorable PK/toxicology supporting clinical evaluation. (oncologypro.esmo.org)

Clinical development

• Phase 1a/1b (NCT06179069): global, open‑label dose‑escalation and expansion evaluating ZL‑1310 as monotherapy and in combinations (with atezolizumab ± carboplatin) in ES‑SCLC across lines of therapy. (cdek.pharmacy.purdue.edu)
• Additional Phase Ib/II study in selected DLL3+ solid tumors (neuroendocrine carcinomas) initiated in 2025 (NCT06885281). (clinicaltrials.ucsf.edu)

Efficacy

• ASCO 2025 update (dose escalation + expansion; n=89 enrolled; 2L cohort highlighted):
• 2L SCLC ORR 67% across all doses (n=33); ORR 79% at 1.6 mg/kg (n=14).

• Median duration of response (DoR) not reached at cutoff; 29/38 responders remained on study.
  These data informed selection of a sub‑2.0 mg/kg dose and plans for a pivotal 2L trial in 2025. (nasdaq.com)

• ENA 2024 (early monotherapy dose‑escalation; n=25 treated; 19 response‑evaluable):

• ORR 74% (all partial responses) with responses across DLL3 expression levels (H‑score range 5–260); none in the DLL3‑negative tumor.
• All 6 evaluable patients with baseline brain metastases achieved PR.
  Follow‑up was short at that cutoff (median 2.4 months). (businesswire.com)

Note: As of October 7, 2025, peer‑reviewed, full manuscripts of ZL‑1310 clinical results have not been identified; efficacy data are from conference presentations and company disclosures.

Safety

• ASCO 2025 (n=89):
• At target doses <2.0 mg/kg: Grade ≥3 treatment‑related adverse events (TRAEs) 6%; serious TRAEs 4%; common TRAEs included anemia and neutropenia; no treatment discontinuations and no Grade ≥3 ILD reported in this dose range.

• Across all dose cohorts: Grade ≥3 TRAEs 23%; serious TRAEs 21%; five discontinuations due to TRAEs occurred only in higher‑dose cohorts (≥2.0 mg/kg). Two Grade ≥3 treatment‑related ILD events were reported at 2.0 and 2.4 mg/kg. (ir.zailaboratory.com)

• ENA 2024 (n=25): most TEAEs were Grade 1–2; Grade ≥3 treatment‑related events in 20% (neutropenia most common); one DLT (Grade 4 transient neutropenia/thrombocytopenia) at 2.4 mg/kg; no discontinuations due to TEAEs. (businesswire.com)

Regulatory and status highlights

• Orphan Drug designation (SCLC): January 22, 2025. (ir.zailaboratory.com)
• Fast Track designation (ES‑SCLC): May 19, 2025. (ir.zailaboratory.com)
• Pivotal 2L ES‑SCLC study planned to start in 2025 based on Phase 1 profile. (ir.zailaboratory.com)

Further reading

• ZL‑1310 ASCO 2025 data update (company summary). (nasdaq.com)
• ENA 2024 oral presentation summary for early Phase 1 results. (businesswire.com)
• Preclinical characterization of ZL‑1310 (ELCC 2024 abstract 241P). (oncologypro.esmo.org)
• FDA Fast Track designation announcement (May 19, 2025). (ir.zailaboratory.com)
• FDA Orphan Drug designation announcement (Jan 22, 2025). (ir.zailaboratory.com)
• Trial synopsis and design details (NCT06179069). (cdek.pharmacy.purdue.edu)
• Additional Phase Ib/II study in DLL3+ solid tumors (NCT06885281). (clinicaltrials.ucsf.edu)

Caveats: Reported response rates and safety findings are from an ongoing early‑phase program with evolving follow‑up; confirmatory evidence from the planned pivotal study will be needed to establish benefit–risk and optimal dosing in 2L ES‑SCLC. (ir.zailaboratory.com)

Last updated: Oct 2025