Zai Lab (ZLAB) American Society of Clinical Oncology Annual Meeting 2025 summary

Key clinical data and insights

• Phase I study of ZL1310 in recurrent small cell lung cancer showed robust efficacy, with a confirmed ORR of 68% and disease control rate of 93% in dose escalation cohorts, and particularly strong results at the 1.6 mg/kg dose level.

• Safety profile was favorable, with low rates of high-grade adverse events and manageable toxicity; grade 3+ ILD was rare and mostly associated with higher doses (≥2.0 mg/kg).

• Efficacy was notable in patients with brain metastases, with an ORR of 68% in this subgroup and up to 86% in those without prior cranial radiation.

• Rapid onset of response was observed, with a median time to response of 5.6 weeks and durable responses, some ongoing beyond nine months.

• The 1.6 mg/kg dose is being advanced for phase III based on its balance of efficacy and tolerability, pending further FDA discussions.

Development strategy and regulatory plans

• A randomized phase III trial in second-line small cell lung cancer is planned for the second half of the year, comparing ZL1310 to investigator's choice of therapy, with overall survival as the primary endpoint.

• Accelerated approval will be sought based on confirmed ORR, with secondary endpoints including duration of response, PFS, safety, and quality of life; interim readout expected next year and potential approval in 2027.

• Combination studies in first-line small cell lung cancer are underway, including regimens with carboplatin and atezolizumab, aiming to reduce chemotherapy burden.

• Expansion into other DLL3-expressing neuroendocrine carcinomas is planned, with a phase I/registrational study targeted for this year.

• Ongoing dialogue with FDA focuses on finalizing dose selection and study design, with fast track designation already granted.

Competitive landscape and future outlook

• ZL1310 is positioned as a best-in-class DLL3-targeted ADC, with advantages in ease of administration and safety compared to Tarlatamab and other ADCs.

• Durability of response is considered clinically meaningful, with over half of responders maintaining benefit at six months or longer in mature cohorts.

• The agent has shown activity in patients previously treated with Tarlatamab, supporting potential sequencing or combination strategies.

• Vigilance for ILD is emphasized, but incidence is comparable to other ADCs in lung cancer; dose and prior radiation are key risk factors.

• The program aims for broad impact across high-need tumor types, with the first regulatory submission targeted as early as next year.