Zai Lab (ZLAB) Study update summary

Intracranial efficacy in small cell lung cancer

• Zoci (ZL-1310), a DLL3-targeting ADC, showed a 54% intracranial response rate in extensive-stage small cell lung cancer patients with brain metastases, with 62% response at the 1.6 mg/kg dose.

• Seven complete intracranial responses were observed across all doses, with a 25% complete response rate at 1.6 mg/kg.

• Responses were rapid (most seen at first assessment, ~6 weeks) and durable, with two-thirds ongoing at a median of 9 months.

• Efficacy was observed regardless of prior brain radiotherapy: 60% response in non-irradiated and 50% in irradiated patients, indicating a direct drug effect.

• Safety profile was favorable and manageable, with grade 3+ adverse events in 15% at the 1.6 mg/kg dose and no intracranial complications reported.

Activity in extrapulmonary neuroendocrine carcinomas (EPNEC/epNEC)

• In a phase Ib/II study, zoci achieved a 38% overall response rate and 56% disease control rate in EPNEC patients post-platinum chemotherapy.

• Responses were seen across multiple NEC subtypes, including both DLL3-positive and DLL3-negative tumors, and in patients with aggressive disease.

• Response rates were 33% in gastroenteropancreatic NECs and 44% in other extrapulmonary NECs.

• Durable responses were observed, with some lasting over six months.

• Safety was consistent with SCLC, with mostly low-grade hematologic and GI events, and grade ≥3 adverse events in 30.4% of patients.

Clinical development and combination strategies

• A global phase III DLLEVATE/DELLEVATE trial is ongoing, comparing zoci to standard therapies in second-line and beyond, with primary endpoints of objective response rate and overall survival.

• Multiple pivotal and combination studies are planned or ongoing, including combinations with T-cell engagers and PD-L1 inhibitors in SCLC and EPNEC.

• Combination approaches aim to leverage zoci’s cytotoxicity with immune-mediated therapies for deeper, more durable responses.

• Interim analysis for accelerated approval in SCLC is expected in 2028, with pivotal first-line trials planned.

• Zoci is positioned as a potential new standard of care in both SCLC and EPNEC, supported by its safety and efficacy profile.