A Study of ZL-1310 in Subjects With Small Cell Lung Cancer

An Open-label, Multicenter Study of ZL-1310 to Evaluate the Safety, Efficacy, and Pharmacokinetics in Participants With Small Cell Lung Cancer

An open-label, multicenter study of ZL-1310 as a single agent and in combination with Atezolizumab (with and without Carboplatin) to evaluate the safety, efficacy, and pharmacokinetics in subjects with small cell lung cancer

Study Overview

• Status: Recruiting
• Conditions: SCLC
• Intervention / Treatment: Drug: ZL-1310; Drug: Atezolizumab; Drug: Carboplatin

Detailed Description

This is an open-label, ascending, multiple-dose, phase 1 study evaluating ZL-1310 as a single agent, in combination with Atezolizumab, and in combination with Atezolizumab and Carboplatin in subjects with extensive SCLC.

• Study Type: Interventional
• Enrollment (Estimated): 339
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mona Qureshi; Email: Study-ZL-1310-001@zailaboratory.com
• Study Contact Backup: Name: Erin Nurre; Phone Number: 8596094423; Email: Study-ZL-1310-001@zailaboratory.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • Recruiting
      • Zai Lab Site 1004
      • Contact: Site 1004
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Zai Lab Site 1005
      • Contact: Site 1005
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Not yet recruiting
      • Zai Lab Site 1012
      • Contact: Site 1012
  • Guangdong
    • Guangzhou, Guangdong, China, 510030
      • Recruiting
      • Zai Lab Site 1001
      • Contact: Site 1001
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Not yet recruiting
      • Zai Lab Site 1009
      • Contact: Site 1009
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Zai Lab Site 1006
      • Contact: Site 1006
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Zai Lab 1002
      • Contact: Site 1002
  • Hunan
    • Changsha, Hunan, China, 410013
      • Not yet recruiting
      • Zai Lab Site 1014
      • Contact: Site 1014
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Zai Lab Site 1016
      • Contact: Site 1016
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • Zai Lab Site 1003
      • Contact: Site 1003
  • Jilin
    • Ch’ang-ch’un, Jilin, China, 130012
      • Recruiting
      • Zai Lab Site 1008
      • Contact: Site 1008
  • Liaoning
    • Shenyang, Liaoning, China, 110041
      • Not yet recruiting
      • Zai Lab Site 1017
      • Contact: Site 1017
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Not yet recruiting
      • Zai Lab Site 1015
      • Contact: Site 1015
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Zai Lab Site 1011
      • Contact: Site 1011
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Zai Lab Site 1010
      • Contact: Site 1010
  • Sichaun
    • Chengdu, Sichaun, China, 610041
      • Recruiting
      • Zai Lab Site 1013
      • Contact: Site 1013
• Spain
  • Barcelona, Spain, 08023
    • Not yet recruiting
    • Zai Lab Site 8007
    • Contact: Site: 8007
  • Madrid, Spain, 28050
    • Not yet recruiting
    • Zai Lab Site 8009
    • Contact: Site: 8009
  • Málaga, Spain, 29010
    • Not yet recruiting
    • Zai Lab Site 8008
    • Contact: Site: 8008
  • Pozuelo de Alarcón, Spain, 28223
    • Not yet recruiting
    • Zai Lab Site 8010
    • Contact: Site: 8010
  • Seville, Spain, 41013
    • Not yet recruiting
    • Zai Lab Site 8011
    • Contact: Site: 8011
  • Barcelona
    • Barcelona, Barcelona, Spain, 8035
      • Recruiting
      • Zai Lab Site 8002
      • Contact: Site: 8002
  • Madrid
    • Madrid, Madrid, Spain, 28034
      • Recruiting
      • Zai Lab Site 8003
      • Contact: Site: 8003
    • Madrid, Madrid, Spain, 28041
      • Recruiting
      • Zai Lab Site 8006
      • Contact: Site: 8006
  • Sevilla
    • Seville, Sevilla, Spain, 41009
      • Recruiting
      • Zai Lab Site 8005
      • Contact: Site: 8005
  • Valencia
    • Valencia, Valencia, Spain, 46010
      • Recruiting
      • Zai Lab Site 8004
      • Contact: Site: 8004
    • Valencia, Valencia, Spain, 46026
      • Recruiting
      • Zai Lab Site 8001
      • Contact: Site: 8001
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • Zai Lab Site 2005
      • Contact: Site 2005
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Zai Lab Site 2030
      • Contact: Site 2030
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Zai Lab Site 2026
      • Contact: Site 2026
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Zai Lab Site 2013
      • Contact: Site 2013
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Zai Lab Site 2001
      • Contact: Site 2001
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Zai Lab Site 2002
      • Contact: Site 2002
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Zai Lab Site 2018
      • Contact: Site 2018
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Zai Lab Site 2024
      • Contact: Site 2024
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Not yet recruiting
      • Zai Lab Site 2029
      • Contact: Site 2029
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Zai Lab Site 2012
      • Contact: Site 2012
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Zai Lab Site 2006
      • Contact: Site 2006

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent
• Participant with metastatic or extensive-stage small cell lung cancer (de novo, not transformed) and for Part 1A and 1B must have documented disease progression during or following a platinum-based chemotherapy regimen. For Part 1C and Part 4, no prior systemic treatment for SCLC (including chemoradiotherapy for limited-stage SCLC). For Part 1B backfill and Part 3, first-line setting: no prior systemic treatment for SCLC (including chemoradiotherapy for limited-stage SCLC); or, first-line maintenance setting: participants have received at least 4 cycles of 1L induction therapy with carboplatin or cisplatin, etoposide, and anti-PD-L1 inhibitor for ES-SCLC with ongoing CR, PR, or SD per RECIST v1.1 assessed by the investigator. For Part 2-1, participants must have received no more than 2 lines of prior therapies in the extensive-stage setting, and progressed on or after a platinum-based chemotherapy regimen AND an anti-DLL3 T-cell engager (TCE). For Part 3, participants have received at least 4 cycles of 1L induction therapy with carboplatin or cisplatin etoposide, and anti-PD-L1 inhibitor for ES-SCLC with ongoing CR, PR, or SD per RECIST v1.1 assessed by the investigator.
• Adult men and women ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subjects must have at least one measurable target lesion as defined by RECIST v1.1 on CT, PET/CT, or MRI.
• Subjects must be willing to undergo a tumor biopsy or must provide archived tumor tissue sample at screening per protocol guidelines.
• Life Expectancy >/= 3 months.

Exclusion Criteria:

• Participants with another known malignancy that is progressing or requires active treatment within the last 2 years. Exceptions: basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin with previously administered curative treatment, in situ cervical cancer, or other cancers that do not require systemic anti-cancer therapies and will not impact life expectancy.

• Symptomatic or untreated brain metastasis requiring concurrent treatment. For Part 2, Part 3, and Part 4 the following subjects can be enrolled if they have a stable neurologic status for at least 2 weeks prior to the first dose of ZL-1310:

  1. Subjects with untreated and asymptomatic brain metastases.
  2. Subjects with treated brain metastases that are no longer symptomatic (i.e. without neurologic signs or symptoms), who require no treatment with steriods or anticonvulsants and have recovered from the actue toxic effects of radiotherapy.
• Subjects with leptomeningeal disease.
• Treatment with any systemic anti-cancer treatment or other investigational products/ device within 3 weeks before first dose of study treatment.
• Non-palliative radiotherapy within 2 weeks prior to first dose of study treatment or have had a history of radiation pneumonitis.
• Major surgery within 4 weeks of the first dose of study treatment.
• Hypersensitivity to any ingredient of the study treatment.
• Inadequate organ function (as defined in protocol) within 10 days prior to the first dose of study treatment,
• Participants with a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 14 days or 5 half-lives before the first dose of study treatment, whichever is longer.
• Participants have received a live or live-attenuated vaccine within 30 days of planned start of study therapy.
• Impaired cardiac function or clinically significant cardiac disease within the last 3 months before administration of the first dose of the study treatment
• Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue, or inflammatory disorders, including but not limited to pneumonitis.
• Pregnant or nursing (lactating) women.
• Participants who have been on concomitant strong CYP3A or CYP2D6 inhibitors within 14 days or 5 half-lives before the first study treatment, whichever is longer.
• For Part 1C and Part 4 (ZL-1310 in combination with Atezolizumab and Carboplatin), participants who received prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
• For Part 1B (ZL-1310 in combination with Atezolizumab) and Part 1C (ZL-1310 in combination with Atezolizumab and Carboplatin), participants who received systemic immunostimulatory agents (including but not limited to, IFNs and IL2) within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to the initiation of study treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: Part 1A; ZL-1310 as a single-agent	Drug: ZL-1310; Drug: ZL-1310
Experimental: Dose Expansion: Part 1B; ZL-1310 in combination with Atezolizumab	Drug: ZL-1310; Drug: ZL-1310; Drug: Atezolizumab; Drug Atezolizumab
Experimental: Dose Escalation: Part 1C; ZL-1310 in combination with Atezolizumab and Carboplatin as induction and followed by ZL-1310 and Atezolizumab as maintenance	Drug: ZL-1310; Drug: ZL-1310; Drug: Atezolizumab; Drug Atezolizumab; Drug: Carboplatin; Drug Carboplatin
Experimental: Dose Expansion: Arm 1 (Part 2); Dose level 1 of ZL-1310 established from single-agent dose-escalation	Drug: ZL-1310; Drug: ZL-1310
Experimental: Dose Expansion: Arm 2 (Part 2); Dose level 2 of ZL-1310 established from single-agent dose escalation	Drug: ZL-1310; Drug: ZL-1310
Experimental: Dose Extension: Arm 1 (Part 2); ZL-1310 as a single agent	Drug: ZL-1310; Drug: ZL-1310
Experimental: Doublet Dose Optimization: Arm 1 (Part 3A); Dose level 1 of ZL-1310 established from single agent dose escalation, in combination with Atezolizumab	Drug: ZL-1310; Drug: ZL-1310; Drug: Atezolizumab; Drug Atezolizumab
Experimental: Doublet Dose Optimization: Arm 2 (Part 3A); Dose level 2 of ZL-1310 established from single agent dose escalation in combination with Atezolizumab	Drug: ZL-1310; Drug: ZL-1310; Drug: Atezolizumab; Drug Atezolizumab
Experimental: Triplet Dose Optimization: Arm 1 (Part 4A); Dose level 1 of ZL-1310 established from single agent dose escalation in combination with Atezolizumab + Carboplatin induction followed by ZL-1310 + Atezolizumab as maintenance	Drug: ZL-1310; Drug: ZL-1310; Drug: Atezolizumab; Drug Atezolizumab; Drug: Carboplatin; Drug Carboplatin
Experimental: Triplet Dose Optimization: Arm 2 (Part 4A); Dose level 2 of ZL-1310 established from single agent dose escalation, in combination with Atezolizumab + Carboplatin induction followed by ZL-1310 + atezolizumab as induction	Drug: ZL-1310; Drug: ZL-1310; Drug: Atezolizumab; Drug Atezolizumab; Drug: Carboplatin; Drug Carboplatin
Experimental: Dose Extension: Part 2-1; single-agent dose extension for Post-anti-DLL3	Drug: ZL-1310; Drug: ZL-1310
Experimental: Doublet Dose Extension: Part 3B; Doublet dose extension for 1L maintenance only OR 1L induction + maintenance; to be initiated at the discretion of the sponsor based on the available emerging data.	Drug: ZL-1310; Drug: ZL-1310; Drug: Atezolizumab; Drug Atezolizumab
Experimental: Triplet Dose Extension: Part 4B; Triplet dose extension for 1L induction + maintenance; to be initiated at the discretion of the sponsor based on the available emerging data.	Drug: ZL-1310; Drug: ZL-1310; Drug: Atezolizumab; Drug Atezolizumab; Drug: Carboplatin; Drug Carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicities of ZL-1310 as a single agent (Part 1A), in combination with Atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C)	Number of subjects with Dose Limiting Toxicities (DLTs)	up to 24 months
Incidence of Treatment Emergent Adverse-Events of ZL-1310 as a single agent (Part 1A), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C)	Number of subjects with treatment-emergent adverse events (TEAEs)	up to 24 months
Incidence of Serious Adverse Events of ZL-1310 as a single agent (Part 1A), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C)	Number of subjects with serious adverse events	up to 24 months
Incidence of Treatment Emergent Adverse Events of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3) and in combination with atezolizumab and carboplatin (Part 4)	Number of subjects with treatment emergent adverse events leading to dose modifications and/or study treatment discontinuation	up to 24 months
Incidence of Serious Adverse-Events (SAEs) of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3), and in combination with atezolizumab and carboplatin (Part 4)	Number of subjects with serious adverse events	up to 24 months
Antitumor activity per RECIST v1.1 by investigator's assessment of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3), and in combination with atezolizumab and carboplatin (Part 4)	antitumor activity per RECIST v1.1 by investigator's assessment	up to 24 months
Objective response rate (ORR) per RECIST v1.1 of ZL-1310 as a single agent (Part 2) and in combination with atezolizumab and carboplatin (Part 4)	objective response rate per RECIST v1.1	up to 24 months
Disease control rate (DCR) per RECIST v1.1 of ZL-1310 in combination with atezolizumab	disease control rate per RECIST v1.1	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) per RECIST 1.1 of ZL-1310 as a single agent (Part 1A) in combination with atezolizumab (Part 1B), in combination with atezolizumab and carboplatin (Part 1C, Part 3)	Objective Response Rate (ORR) per RECIST 1.1	up to 24 months
Disease control rate (DCR) per RECIST v1.1 of ZL-1310 as a single agent (Part 1A and Part 2), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 4)	Disease control rate (DCR) per RECIST v1.1	up to 24 months
Duration of response per RECIST v1.1	Duration of response per RECIST v1.1	up to 24 months
Progression free survival per RECIST v1.1	Progression free survival per RECIST v1.1	up to 24 months
Overall Survival of ZL-1310	Overall Survival of ZL-1310	up to 24 months
Pharmacokinetics: Total Antibody of ZL-1310	Pharmacokinetics: Total Antibody of ZL-1310	up to 24 months
Pharmacokinetics: Unconjugated payloads of ZL-1310	Pharmacokinetics: Unconjugated payloads of ZL-1310	up to 24 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): December 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 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; Coordination Complexes; Carboplatin; atezolizumab
• Other Study ID Numbers: ZL-1310-001

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
• product manufactured in and exported from the U.S.: No