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NCT06179069PHASE1Recruiting

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

Zai Lab (Shanghai) Co., Ltd.

Start Date

1/23/2024

Completion Date

7/31/2027

Summary

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

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

ZL-1310

DRUG

Atezolizumab

DRUG

Carboplatin

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Conditions

SCLC

Locations

Zai Lab Site 2005

Duarte, California 91010

United States

Zai Lab Site 2030

New Haven, Connecticut 06519

United States

Zai Lab Site 2026

Sarasota, Florida 34232

United States

Zai Lab Site 2013

Detroit, Michigan 48201

United States

Zai Lab Site 2001

Hackensack, New Jersey 07601

United States

Zai Lab Site 2002

Buffalo, New York 14263

United States

Zai Lab Site 2018

Durham, North Carolina 27710

United States

Zai Lab Site 2024

Cleveland, Ohio 44106

United States

Zai Lab Site 2029

Pittsburgh, Pennsylvania 15232

United States

Zai Lab Site 2012

Charleston, South Carolina 29425

United States

Zai Lab Site 2006

Fairfax, Virginia 22031

United States

Zai Lab Site 1004

Hefei, Anhui 230022

China

Zai Lab Site 1005

Beijing, Beijing Municipality 100142

China

Zai Lab Site 1012

Xiamen, Fujian 361000

China

Zai Lab Site 1001

Guangzhou, Guangdong 510030

China

Zai Lab Site 1009

Harbin, Heilongjiang 150000

China

Zai Lab Site 1006

Zhengzhou, Henan 450008

China

Zai Lab 1002

Wuhan, Hubei 430022

China

Zai Lab Site 1014

Changsha, Hunan 410013

China

Zai Lab Site 1016

Nanjing, Jiangsu 210008

China

Zai Lab Site 1003

Nanchang, Jiangxi 330006

China

Zai Lab Site 1008

Ch’ang-ch’un, Jilin 130012

China

Zai Lab Site 1017

Shenyang, Liaoning 110041

China

Zai Lab Site 1015

Xi'an, Shaanxi 710061

China

Zai Lab Site 1011

Jinan, Shandong 250000

China

Zai Lab Site 1010

Shanghai, Shanghai Municipality 200032

China

Zai Lab Site 1013

Chengdu, Sichaun 610041

China

Zai Lab Site 8002

Barcelona, Barcelona 8035

Spain

Zai Lab Site 8003

Madrid, Madrid 28034

Spain

Zai Lab Site 8006

Madrid, Madrid 28041

Spain

Zai Lab Site 8005

Seville, Sevilla 41009

Spain

Zai Lab Site 8004

Valencia, Valencia 46010

Spain

Zai Lab Site 8001

Valencia, Valencia 46026

Spain

Zai Lab Site 8007

Barcelona, 08023

Spain

Zai Lab Site 8009

Madrid, 28050

Spain

Zai Lab Site 8008

Málaga, 29010

Spain

Zai Lab Site 8010

Pozuelo de Alarcón, 28223

Spain

Zai Lab Site 8011

Seville, 41013

Spain