The DLL3-targeting ADC ZL-1310 demonstrates favorable objective response rate and safety in extensive-stage small cell lung cancer.

Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today presented data from the ongoing global Phase 1a clinical study of ZL-1310 in an oral plenary session at the 2024 EORTC-NCI-AACR (ENA) Congress held in Barcelona, Spain. ZL-1310 is a potential best-in-class next-generation antibody-drug conjugate (ADC) targeting Delta-like ligand 3 (DLL3), which is aberrantly expressed in over 85% of small cell lung cancers (SCLC)^[1]-[4] but rarely in healthy tissues. ZL-1310 is being studied in patients with extensive-stage small cell lung cancer (ES-SCLC) who have previously received at least one platinum-based chemotherapy regimen.

The presentation at the ENA Congress reported data from the ongoing Phase 1a monotherapy dose-escalation study, including results from 25 patients across four dose groups (0.8 mg/kg, 1.6 mg/kg, 2.0 mg/kg, and 2.4 mg/kg). Tumor responses were evaluable in 19 patients.

Key efficacy results (n=19) included:

An objective response rate (ORR) of 74% (95% CI: 48.8, 90.9) in patients evaluated after at least one treatment. ZL-1310 demonstrated antitumor activity across all dose levels;
All patients with a DLL3 H-Score >5 (range: 5–260) showed tumor response. No responses were observed in patients without DLL3 expression;
With a median follow-up of 2.3 months across all dose groups, duration of response could not be assessed. Of the 14 responders among 19 patients, 13 remained on treatment;
All six patients with baseline brain metastases who underwent at least one post-baseline tumor assessment achieved partial response (PR);
One patient who progressed after DLL3 bispecific therapy achieved PR at the first tumor assessment.

Key safety results (n=25) included:

ZL-1310 was well-tolerated at all dose levels, with most treatment-emergent adverse events (TEAEs) being Grade 1 or 2. A dose-limiting toxicity (DLT) (Grade 4 transient neutropenia/thrombocytopenia) was observed at 2.4 mg/kg. Five of 25 patients (20%) experienced Grade ≥3 treatment-related adverse events (TRAEs); the most common Grade ≥3 TRAE was neutropenia (3/25 patients, 12%). Two patients (8%) had serious TRAEs; three (12%) required dose reduction, with no treatment discontinuations due to TEAEs.

All 19 patients had progressed after standard platinum chemotherapy, and 92% had progressed after immune checkpoint inhibitors. Fifty-six percent had failed ≥2 prior therapies. Twenty-eight percent had baseline brain metastases. As of the October 10, 2024 data cutoff, all 19 patients had ≥1 post-baseline tumor assessment per RECIST v1.1, with 16 having H-Scores for DLL3 expression.

Dr. Alex Spira, Medical Oncologist at Virginia Cancer Specialists and NEXT Oncology, stated: "Preliminary results from the ongoing Phase 1 study of ZL-1310 suggest this next-gen ADC may induce antitumor responses in most ES-SCLC patients with favorable tolerability. These findings are particularly encouraging given the urgent unmet need in this population. The promising data support continued evaluation of ZL-1310 as monotherapy in the dose-expansion phase of the ongoing Phase 1 study and in combination regimens."

Dr. Rafael G. Amado, President and Global Head of R&D at Zai Lab, commented: "The ZL-1310 clinical program reflects Zai Lab's unwavering commitment and demonstrated capability in exploring innovative therapies against validated oncology targets to advance our global pipeline. Building on these exciting Phase 1 results, we look forward to further developing ZL-1310 as part of our oncology portfolio and advancing this promising candidate across multiple treatment lines."