Zai Lab’s zocilurtatug pelitecan plus atezolizumab achieved an 81.8% response rate and 81.9% six-month PFS in first-line extensive-stage small cell lung cancer.
Written By: Creola Gonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
Zai Lab’s investigational DLL3-targeting antibody-drug conjugate zocilurtatug pelitecan (zoci) achieved an 81.8% confirmed response rate and an estimated 81.9% six-month progression-free survival rate when combined with atezolizumab in first-line extensive-stage small cell lung cancer (ES-SCLC). The chemotherapy-free regimen showed encouraging durability and a low rate of severe zoci-related adverse events in an early-stage clinical trial.
High Response Rates with the Chemotherapy-Free Doublet
The Phase 1b study evaluated zoci plus atezolizumab, with or without carboplatin, as first-line treatment for ES-SCLC. At the recommended Phase 3 dose of 1.6 mg/kg, the doublet produced a confirmed objective response rate (ORR) of 81.8% (27 of 33 patients; 95% CI, 64.5% to 93.0%), based on investigator assessment. The estimated six-month progression-free survival (PFS) rate was 81.9%.
Among 15 patients with at least six months of follow-up, median PFS and median duration of response had not been reached after a median follow-up of 10 months. Ten patients (66.7%) remained alive without disease progression at the September 2026 data cutoff.
These findings suggest that the combination may provide sustained disease control, although the small patient population and limited follow-up prevent firm conclusions about long-term efficacy.
DLL3 Targeting Supports a Platinum-Free Strategy
Zoci is an investigational antibody-drug conjugate (ADC) targeting delta-like ligand 3 (DLL3), a protein overexpressed in small cell lung cancer and associated with poor clinical outcomes. The approach delivers a cytotoxic payload to DLL3-expressing cancer cells.
Current first-line treatment for ES-SCLC typically combines platinum-based chemotherapy with a checkpoint inhibitor. Although this approach produces initial responses in many patients, disease progression often occurs within months, and treatment can cause substantial toxicity.
A regimen combining zoci with atezolizumab, a PD-L1 inhibitor, could offer an alternative without platinum chemotherapy. However, the Phase 1b results do not establish superiority over standard treatment because the study did not directly compare the regimens in a randomized trial.
Safety Profile and Carboplatin Combination
At the 1.6 mg/kg dose, zoci plus atezolizumab was generally well tolerated. Grade 3 or higher adverse events attributed to zoci occurred in three of 33 patients (9.1%). No treatment-related discontinuations occurred, and investigators reported one case of Grade 1 interstitial lung disease or pneumonitis.
The most common zoci-related adverse events of any grade were anemia (48.5%), nausea (36.4%), leukopenia (30.3%), decreased appetite, elevated alanine aminotransferase and neutropenia (27.3% each), and lymphopenia (21.2%). Most adverse events were Grade 1 or 2 and non-serious.
A separate group of 13 patients receiving zoci, atezolizumab and carboplatin across multiple dose levels achieved an objective response rate of 92.3%. Median progression-free survival was 8.4 months, and median duration of response was 7.7 months. However, Grade 3 or higher treatment-emergent adverse events from any cause occurred in 76.9% of patients receiving the triplet, compared with 21.2% in the doublet group. In the doublet group, Grade 3 or higher adverse events specifically attributed to zoci occurred in 9.1% of patients (3/33). These findings indicate a higher observed rate of severe treatment-emergent adverse events with the carboplatin-containing regimen, although differences in treatment groups and dose levels limit direct comparisons.
Global Phase 3 Trial Planned for 2026
Zai Lab plans to initiate a global, randomized Phase 3 trial of zoci combined with an immuno-oncology regimen in first-line ES-SCLC by the end of 2026. The company is also evaluating zoci in the Phase 3 DLLEVATE study in previously treated ES-SCLC and in a Phase 1/2 trial involving neuroendocrine carcinomas and other DLL3-positive solid tumors.
The upcoming Phase 3 study will be critical to determine whether the high response rate and encouraging durability observed with zoci plus atezolizumab translate into a meaningful clinical benefit relative to established first-line treatment.
Reference
Zai Lab’s Zocilurtatug Pelitecan (Zoci, Formerly ZL-1310) Demonstrates High Response Rates, Encouraging Durability and Well-Tolerated Safety Profile in First-Line Extensive-Stage Small Cell Lung Cancer, Zai Lab, 23 October 2026
A Study of ZL-1310 in Subjects with Small Cell Lung Cancer, ClinicalTrials.gov ID NCT06179069
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content