Zai Lab Reports Broad Tumour Responses With Zocilurtatug in epNEC

Zai Lab Limited reported updated Phase 1b/2 results showing that zocilurtatug pelitecan (zoci), an investigational DLL3-targeting antibody-drug conjugate (ADC), achieved a confirmed objective response rate (ORR) of 40.0% in patients with previously treated advanced extrapulmonary neuroendocrine carcinomas (epNECs). The findings also showed a median duration of response (DOR) of 5.6 months, with treatment-related discontinuation reported in less than 1% of patients.

Updated Phase 1b/2 Results Demonstrate Activity Across epNEC Subtypes

The findings come from the Phase 1b/2 clinical trial (NCT06885281), evaluating zoci, formerly known as ZL-1310, in patients with advanced or metastatic epNECs whose disease progressed during or after platinum-based chemotherapy.

Zoci is an investigational ADC targeting Delta-like ligand 3 (DLL3), a protein expressed in small cell lung cancer and other neuroendocrine carcinomas. The study evaluated intravenous zoci monotherapy at 1.6 mg/kg every three weeks. Tumour responses were assessed using investigator-assessed RECIST v1.1, with additional assessments for certain neuroendocrine carcinomas.

In the primary efficacy population of 60 patients, investigator-assessed confirmed ORR was 40.0% (24/60; 95% confidence interval [CI]: 27.6%–53.5%), while the disease control rate (DCR) reached 55.0% (33/60; 95% CI: 41.6%–67.9%).

Responses were observed across different tumour subtypes. Patients with gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) achieved a confirmed ORR of 35.9% (14/39; 95% CI: 21.2%–52.8%), compared with 47.6% (10/21; 95% CI: 25.7%–70.2%) among patients with other epNEC subgroups.

The median DOR was 5.6 months (95% CI: 3.0–9.3). Among 18 responders with at least six months of follow-up opportunity from their initial response, six (33.3%) remained in response or had maintained a response for at least six months.

The updated findings were consistent with previously reported AACR 2026 results. However, recently enrolled Phase 2 participants were not sufficiently mature for efficacy analysis, and additional follow-up remains ongoing.

Safety Profile Shows Low Treatment-Related Discontinuation

The safety analysis included all 133 patients enrolled in the study. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 12.8% (17/133) of patients, while Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported in 29.3% (39/133).

Among Grade 3 or higher TEAEs, anaemia (5.3%; 7/133) and neutropenia (3.8%; 5/133) were the most frequently reported.

Interstitial lung disease (ILD)/pneumonitis occurred in two patients (1.5%), with both cases classified as Grade 2. No Grade 3 or higher ILD/pneumonitis events were observed.

Treatment-related discontinuation occurred in one patient (0.8%). One participant in the Phase 2 cohort experienced a fatal TEAE, which the investigator determined was unrelated to zoci. No treatment-related deaths were reported.

Although the low discontinuation rate is encouraging, the incidence of Grade 3 or higher TRAEs warrants continued safety assessment as the clinical programme advances.

Zai Lab Advances Potential Accelerated Approval Strategy

Following feedback from the US Food and Drug Administration (FDA), Zai Lab plans to pursue a potential accelerated approval pathway for zoci in previously treated advanced epNECs, based on the single-arm Phase 2 expansion cohort.

The company has completed enrolment in this second-line expansion cohort and expects to report topline results for the full epNEC population in 2027.

Separately, Zai Lab plans to initiate a global Phase 3 trial in 2027 evaluating zoci monotherapy as first-line maintenance treatment for epNECs.

Zoci has received FDA Fast Track designation for epNECs and Orphan Drug Designation for neuroendocrine carcinomas. These designations support clinical development but do not constitute marketing approval.

Clinical Interpretation: DLL3-Targeted ADC Shows Potential in a High-Unmet-Need Setting

The findings provide an encouraging clinical signal for zoci in previously treated advanced epNECs, where no established standard of care exists following progression on or after first-line platinum-based chemotherapy. The 40.0% confirmed ORR, alongside responses across GEP-NEC and other epNEC subgroups, supports further investigation of DLL3-targeted ADC therapy in this setting.

An additional observation was antitumour activity across DLL3 expression levels, including low or absent expression, as assessed by immunohistochemistry. However, these findings do not establish DLL3 expression as a predictive biomarker or clarify which patients are most likely to benefit.

The median DOR of 5.6 months provides an indication of response persistence, although longer follow-up is necessary to establish durability. Similarly, the 0.8% treatment-related discontinuation rate and absence of severe ILD/pneumonitis are relevant safety observations, but the reported Grade 3 or higher TRAEs in 12.8% of patients require continued monitoring.

Importantly, the single-arm design and relatively small primary efficacy population limit comparisons with existing treatments. The planned 2027 expansion-cohort results will be important in determining whether the observed response rate supports a potential accelerated approval submission. The separate Phase 3 programme will evaluate zoci in a different treatment setting, first-line maintenance, and could further define its clinical role in epNECs.

Reference

Zai Lab Presents Updated Clinical Data Demonstrating Zocilurtatug Pelitecan (Zoci) Induces Clinically Meaningful Responses and a Manageable Safety Profile in Previously Treated Extrapulmonary Neuroendocrine Carcinomas, Zai Lab, 05 November 2026

A Study of ZL-1310 in Participants with Selected Solid Tumors, ClinicalTrials.gov ID NCT06885281