Zai Lab Reports Promising Phase 1 Results for Zocilurtatug Pelitecan in Extensive-Stage Small Cell Lung Cancer, Launches Global Phase 3 Trial
Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) has released updated findings from its global Phase 1 clinical trial of zocilurtatug pelitecan (zoci), formerly referred to as ZL-1310, underscoring the drug’s potent anti-tumor activity and durable responses in patients with heavily pre-treated extensive-stage small cell lung cancer (ES-SCLC). The data, which were highlighted as part of an oral presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held from October 22–26, 2025, in Boston, Massachusetts, strengthen zoci’s profile as a promising DLL3-targeted antibody-drug conjugate (ADC) in this difficult-to-treat malignancy.
Dr. Rafael G. Amado, President and Head of Global Research and Development at Zai Lab, emphasized the significance of these findings, stating, “The strong and durable antitumor activity we have observed with zoci, alongside a well-tolerated safety profile, highlights its potential to be a best-in-class DLL3-targeted ADC for small cell lung cancer. Advancing this program from Phase 1 to a global registrational study in under two years reflects the speed, scientific rigor, and executional excellence of our team. It marks a major milestone for Zai Lab as we continue to expand zoci’s development into areas of high unmet need, including first-line SCLC and neuroendocrine carcinoma, both expected to enter registrational phases next year.”
Phase 1 Trial Design and Patient Population
The updated Phase 1 data encompass results from both the monotherapy dose escalation and dose expansion portions of the study, involving 115 patients across six dose cohorts (0.8 mg/kg, 1.2 mg/kg, 1.6 mg/kg, 2.0 mg/kg, 2.4 mg/kg, and 2.8 mg/kg) as of the September 15, 2025 data cut-off. Among these patients, 102 had at least one post-baseline tumor assessment per RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria.
This multicenter trial included patients from the United States, Spain, and China, all of whom had progressed following platinum-based chemotherapy, with 90% having also progressed after prior immune checkpoint inhibitor therapy. Nearly 44% had failed two prior lines of therapy, establishing this cohort as a heavily pre-treated population with limited therapeutic options. Additionally, eleven patients had previously received a DLL3 bi-specific antibody, and 32% had brain metastases at baseline, representing a subgroup traditionally associated with poor prognosis.
Efficacy Results: High Response Rates and Durable Outcomes
The Phase 1 findings reinforce zoci’s efficacy across multiple patient subgroups and dose levels:
- Across all dose cohorts, zoci demonstrated high response rates in patients who progressed on or after platinum-based chemotherapy, and these responses remained consistent over time with extended follow-up.
- In patients receiving zoci as a second-line therapy (n=53), the best overall response rate (ORR) in the 1.6 mg/kg cohort (n=19) reached an impressive 68%.
- Among patients with brain metastases at baseline (n=32), ORR reached 80% in patients who had not received prior brain radiotherapy, indicating notable CNS activity.
- Notably, three of seven patients who progressed after prior tarlatamab treatment responded to zoci, and enrollment for tarlatamab-pretreated patients is ongoing.
- Median duration of response (DoR) across all doses and lines of therapy was estimated at 6.1 months, with median progression-free survival (PFS) of 5.4 months. Responses occurred early, with a median time to confirmed objective response of six weeks, highlighting zoci’s rapid onset of activity.
Enrollment in the dose-finding cohorts continues for the 1.2 mg/kg and 1.6 mg/kg doses, with nearly half of responders still ongoing at the data cut-off, and completion of enrollment is expected in Q4 2025.
Safety Profile: Well-Tolerated Across Doses
Zoci continues to demonstrate a favorable safety profile, particularly at the 1.2 mg/kg and 1.6 mg/kg dose levels:
- In the 1.6 mg/kg cohort, Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 13% of patients, and serious TRAEs occurred in 9%. Importantly, no patients discontinued treatment due to toxicity.
- Two cases of pneumonitis and interstitial lung disease, both Grade 1, were reported among 72 patients treated at 1.2 or 1.6 mg/kg doses.
- Across all dose cohorts, Grade 3 or higher TRAEs occurred in 20% of patients, while serious TRAEs were reported in 8%. The most common high-grade TRAEs were anemia (10%) and neutropenia (11%).
- Five patients discontinued therapy due to TRAEs, all occurring in higher-dose cohorts.
Dr. Grace Dy of Roswell Park Comprehensive Cancer Center, a study investigator, commented, “DLL3 is a validated target in extensive-stage small cell lung cancer, where new therapeutic options are urgently needed due to the aggressive disease course. These Phase 1 results for zoci, showing rapid and sustained responses even in patients with poor prognostic factors, provide compelling clinical evidence that zoci has the potential to be a differentiated DLL3-targeted ADC.”
Phase 3 Registrational Trial: Expanding Global Development
Following the promising Phase 1 results, Zai Lab has initiated a global Phase 3 registrational study of zoci. This multicenter, randomized, open-label trial will enroll approximately 665 patients across North America, Asia, and Europe. The trial is designed to compare the safety and efficacy of zoci versus investigator’s choice therapy (ICT) in patients with relapsed SCLC who have progressed after platinum-based first-line therapy, either as second-line treatment or following one line of chemotherapy and subsequent tarlatamab therapy.
- The primary endpoints include ORR assessed by Blinded Independent Central Review (BICR) per RECIST v1.1 for interim analysis, and overall survival as the primary analysis.
- Secondary endpoints will assess duration of response, progression-free survival, and safety.
Patients and clinicians interested in learning more about the Phase 3 program can visit ClinicalTrials.gov (identifier: NCT07218146).
Upcoming Investor Call and Webcast
Zai Lab will host an investor conference call and webcast on October 24, 2025, at 11 a.m. ET / 11 p.m. HKT, to highlight the updated zoci data presented at the AACR-NCI-EORTC conference and outline next steps in clinical development. Dr. Amado will lead the presentation, which will cover the robust Phase 1 results, safety profile, and the design of the global Phase 3 program.
- Webcast link (preferred registration): Zai Lab Investor Webcast
- Dial-in registration: Conference Call Registration
Oral Presentation at AACR-NCI-EORTC Conference
Dr. Grace Dy delivered the oral presentation entitled: “Phase 1 trial of ZL-1310, a DLL3-targeted ADC, in patients with previously treated extensive-stage small cell lung cancer.” This session, part of Plenary Session 3: Antibody Drug Conjugates, took place on October 24, 2025, at the Hynes Convention Center, Level 3, Ballroom AB, and included a subsequent panel discussion from 9:27 a.m. – 9:45 a.m. ET.
Background on Small Cell Lung Cancer and DLL3-Targeted Therapy
Small cell lung cancer (SCLC) is one of the most aggressive and lethal types of lung cancer, representing approximately 15% of the estimated 2.5 million lung cancer cases diagnosed globally each year. Notably, two-thirds of SCLC patients are diagnosed with extensive-stage disease, which is often resistant to conventional therapy.
DLL3, or delta-like protein 3, is overexpressed in many neuroendocrine tumors, including SCLC, and is associated with poor clinical outcomes. Zocilurtatug pelitecan (zoci) is a DLL3-targeted ADC consisting of a humanized anti-DLL3 monoclonal antibody linked via a cleavable linker to a novel camptothecin derivative, a topoisomerase 1 inhibitor. This innovative ADC is constructed using Zai Lab’s proprietary TMALIN® technology, which leverages the tumor microenvironment to enhance tumor-specific delivery and overcome limitations of first-generation ADCs.
Recognizing its potential, the U.S. FDA granted zoci Orphan Drug Designation in January 2025, highlighting its promise for treating patients with SCLC.
Implications for Patients and the Oncology Community
The updated Phase 1 data underscore zoci’s ability to induce meaningful responses in a heavily pre-treated population, including patients with brain metastases or prior DLL3-targeted therapy. Its early and durable activity, coupled with a manageable safety profile, positions zoci as a potentially transformative therapy in SCLC, a field historically characterized by limited effective options and poor prognosis.
By initiating a large-scale Phase 3 registrational trial, Zai Lab aims to confirm these findings in a global population and potentially set a new standard of care for patients with relapsed or refractory SCLC.
About Zai Lab
Zai Lab (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience, and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health.
For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at https://x.com/ZaiLab_Global.
