A Study of ZL-1310 in Combination With a Checkpoint Inhibitor Versus Standard of Care Platinum Based Chemotherapy With a Checkpoint Inhibitor as First-line Therapy in Participants With Extensive-Stage Small Cell Lung Cancer

A Randomized, Open-Label, Phase 3 Study of ZL-1310, a DLL3 Antibody-drug Conjugate (ADC) in Combination With a Checkpoint Inhibitor Compared to Standard of Care Platinum Based Chemotherapy With a Checkpoint Inhibitor as First-line Therapy in Participants With Extensive-Stage Small Cell Lung Cancer

The purpose of this study is to evaluate the efficacy and safety of ZL-1310 in combination with a checkpoint inhibitor compared to standard first-line therapy in participants with Extensive-Stage Small Cell Lung Cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Extensive-Stage Small Cell Lung Cancer
• Intervention / Treatment: Combination product: ZL-1310 in combination with Atezolizumab or Durvalumab; Combination product: Carboplatin/Etoposide in Combination with Atezolizumab followed by maintenance Atezolizumab with Lurbinectedin; Combination product: Carboplatin/Etoposide or Cistplatin/Etoposide in Combination with Durvalumab induction followed by Durvalumab maintenance

• Study Type: Interventional
• Enrollment (Estimated): 530
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: ZL-1310-005 Study Team; Phone Number: 650-360-1601; Email: Study-ZL-1310-005@zailaboratory.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed ES-SCLC
• No prior systemic therapy has been received
• Medically eligible to receive standard platinum-based chemotherapy with atezolizumab or durvalumab as first-line therapy
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Life expectancy of at least 3 months
• Adequate organ and marrow function

Exclusion Criteria:

• Has a contraindication to receive atezolizumab or durvalumab according to local drug label or local treatment guideline
• Participants with symptomatic CNS metastases (require initiation or dose change of steroids or anti-convulsant within 7 days prior to randomization; require steroid dose higher that prednisone 10 mg/day or equivalent within 14 days prior to randomization
• History of ILD/pnuemonitis (non-infectious) that required corticosteroids, current ILD/pnuemonitis of any grade, or suspected ILD/pnuemonitis that cannot be ruled out by imaging at screening
• Received radiotherapy within 2 weeks to the non-thoracic and within 4 weeks to the thoracic area prior to the first dose of study treatment or received more than 30 Gy of thoracic radiotherapy
• Clinically significant active cardiovascular disease or history of any arterial thromboembolic event within 6 months prior to the first dose of study treatment
• Clinically severe pulmonary compromise (including but not limited to baseline oxygen saturation of <90% on room air) resulting from intercurrent pulmonary illnesses
• Major surgery within 4 weeks prior to the first dose of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZL-1310 in Combination with Checkpoint Inhibitor	Combination product: ZL-1310 in combination with Atezolizumab or Durvalumab; ZL-1310 ADC in combination with checkpoint inhibitor
Active Comparator: Standard of Care Platinum-based Chemotherapy with a Checkpoint Inhibitor	Combination product: Carboplatin/Etoposide in Combination with Atezolizumab followed by maintenance Atezolizumab with Lurbinectedin; Platinum-based chemotherapy in combination with a checkpoint inhibitor; Combination product: Carboplatin/Etoposide or Cistplatin/Etoposide in Combination with Durvalumab induction followed by Durvalumab maintenance; Standard of Care Platinum-based chemotherapy in combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival of ZL-1310 with IO compared to chemo with IO	up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) and by investigator per RECIST v1.1 of ZL-1310 with IO compared to chemo with IO	up to approximately 3 years
Confirmed objective response rate (ORR) assessed by BICR and by investigator per RECIST v1.1 of ZL-1310 with IO compared to chemo with IO	up to approximately 3 years
Duration of response (DoR) assessed by BICR and by the investigator per RECIST v1.1 of ZL-1310with IO compared to chemo with IO	up to approximately 3 years
Time to response (TTR) assessed by BICR and by the investigator per RECIST v1.1 of ZL-1310 with IO compared to chemo with IO	up to approximately 3 years
Confirmed central nervous system response assessed by BICR and by the investigator per modified Response Assessment in Neuro-Oncology for Brain Metastases in participants with brain metastases at baseline of ZL-1310 with IO compared to chemo with IO	up to approximately 3 years
Duration of central nervous system response assessed by BICR and by the investigator per modified Response Assessment in Neuro-Oncology for Brain Metastases in participants with brain metastases at baseline of ZL-1310 with IO compared to chemo with IO	up to approximately 3 years
Incidence rate of new brain metastases in participants without baseline brain metastases of ZL-1310 with IO compared to chemo with IO	up to approximately 3 years
Time to first onset of new brain metastases in participants without baseline brain metastases of ZL-130	up to approximately 3 years
Changes from baseline in quality of life related parameters of ZL-1310 with IO compared to chemo with IO using EQ-5D (EQ-5D-5L index)	up to approximately 3 years
Changes from baseline in quality of life related parameters of ZL-1310 with IO compared to chemo with IO using EQ-5D (EQ visual analog scale [VAS]).	up to approximately 3 years
Changes from baseline in quality of life related parameters of ZL-1310 with IO compared to chemo with IO using EORTC-QLQ-LC13	up to approximately 3 years
Changes from baseline in quality of life parameters of ZL-1310 with IO compared to chemo with IO using EORTC-QLQ-C30	up to approximately 3 years

Collaborators and Investigators

• Sponsor: Zai Lab (Shanghai) Co., Ltd.
• Collaborators: Zai Lab (US) LLC

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2031

Study Registration Dates

• First Submitted: August 24, 2026
• First Submitted That Met QC Criteria: August 26, 2026
• First Posted (Actual): August 31, 2026

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Coordination Complexes; Etoposide; Carboplatin; PM 01183; durvalumab; atezolizumab
• Other Study ID Numbers: ZL-1310-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No