An Open-label, Multicenter Study of ZL-1310 in Subjects With Small Cell Lung Cancer
- Registration Number
- NCT06179069
- Lead Sponsor
- Zai Lab (Shanghai) Co., Ltd.
- Brief Summary
An Open-label, Multicenter Study of ZL-1310 to Evaluate the Safety, Tolerability, 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 85
- Signed informed consent
- Subjects must have histologically or cytologically confirmed metastatic or extensive-stage small cell lung cancer with documented disease progression during or following a platinum-based chemotherapy regimen. No more than 3 prior regimens in the metastatic or extensive stage are allowed.
- 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.
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Subjects 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.
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Symptomatic or untreated brain metastasis requiring concurrent treatment. For Part 2, 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:
- Subjects with untreated and asymptomatic brain metastases.
- 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.
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Subjects with leptomeningeal metastasis.
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Treatment with any systemic anti-cancer treatment or other investigational products/ device within 3 weeks before first dose of study treatment.
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Non-palliative radiotherapy within 2 weeks prior to first dose of study treatment or have had a history of radiation pneumonitis.
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Major surgery within 4 weeks of the first dose of study treatment.
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Hypersensitivity to any ingredient of the study treatment.
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Out of range lab value (as defined in protocol) within 10 days prior to the first dose of study treatment,
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Subjects 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.
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Subjects have received a live or live-attenuated vaccine within 30 days of planned start of study therapy.
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Impaired cardiac function or clinically significant cardiac disease within the last 3 months before administration of the first dose of the study treatment
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Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue, or inflammatory disorders, including not limited to pneumonitis.
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Pregnant or nursing (lactating) women.
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Subjects 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.
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For Part 1C only (ZL-1310 in combination with Atezolizumab and Carboplatin), subjects who received prior treatment with CD137agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
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For Part 1B (Z-1310 in combination with Atezolizumab) and Part 1C (ZL-1310 in combination with Atezolizumab and Carboplatin), subjects who received systemic immunostimulatory agents (including but not limited to, IFNs and IL2) within 4 weeks or 5 drug-elimination half-lives prior to the initiation of study treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation: Arm 1 ZL-1310 ZL-1310 as a single-agent Dose Expansion: Arm 1 ZL-1310 Dose level 1 of ZL-1310 established from single-agent dose-escalation Dose Escalation: Arm 2 Atezolizumab ZL-1310 in combination with Atezolizumab Dose Escalation: Arm 3 Atezolizumab ZL-1310 in combination with Atezolizumab and Carboplatin as induction and followed by ZL-1310 and Atezolizumab as maintenance Dose Escalation: Arm 3 Carboplatin ZL-1310 in combination with Atezolizumab and Carboplatin as induction and followed by ZL-1310 and Atezolizumab as maintenance Dose Extension: Arm 1 ZL-1310 ZL-1310 as a single agent Dose Expansion: Arm 2 ZL-1310 Dose level 2 of ZL-1310 established from single-agent dose-escalation Dose Escalation: Arm 2 ZL-1310 ZL-1310 in combination with Atezolizumab Dose Escalation: Arm 3 ZL-1310 ZL-1310 in combination with Atezolizumab and Carboplatin as induction and followed by ZL-1310 and Atezolizumab as maintenance
- Primary Outcome Measures
Name Time Method Incidence of Dose Limiting Toxicities of ZL-1310 as a single agent up to 24 months Number of subjects with Dose Limiting Toxicities (DLTs)
Incidence of Dose Limiting Toxicities of ZL-1310 in combination with Atezolizumab up to 24 months Number of subjects with Dose Limiting Toxicities (DLTs)
Incidence of Dose-Limiting Toxicities of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months Number of subjects with Dose Limiting Toxicities (DLTs)
Incidence of Treatment Emergent Adverse-Events of ZL-1310 as a single agent up to 24 months Number of subjects with treatment-emergent adverse events (TEAEs)
Incidence of Treatment Emergent Adverse-Events of ZL-1310 in combination with Atezolizumab up to 24 months Number of subjects with treatment-emergent adverse events (TEAEs)
Incidence of Treatment Emergent Adverse Events of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months Number of subjects with treatment-emergent adverse events (TEAEs)
Incidence of Serious Adverse Events of ZL-1310 as a single agent. up to 24 months Number of subjects with serious adverse events (SAEs)
Incidence of Serious Adverse Events of ZL-1310 in combination with Atezolizumab up to 24 months Number of subjects with serious adverse events (SAEs)
Incidence of Serious Adverse Events of ZL-1310 in combination with Atezolizumab and Cabroplatin up to 24 months Number of subjects with serious adverse events (SAEs)
- Secondary Outcome Measures
Name Time Method ORR per RECIST 1.1 of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months Objective Response Rate (ORR) per RECIST 1.1
ORR per RECIST 1.1 of ZL-1310 as a single agent up to 24 months Objective Response Rate (ORR) per RECIST 1.1
ORR per RECIST 1.1 of ZL-1310 in combination with Atezolizumab up to 24 months Objective Response Rate (ORR) per RECIST 1.1
Duration of Response per RECIST 1.1 of ZL-1310 as a single agent up to 24 months Duration of Response per RECIST 1.1
Duration of Response per RECIST 1.1 of ZL-1310 in combination with Atezolizumab up to 24 months Duration of Response per RECIST 1.1
Duration or Response per RECIST 1.1 of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months Duration of Response per RECIST 1.1
PFS per RECIST 1.1 of ZL-1310 as a single agent up to 24 months Progression free survival (PFS) per RECIST 1.1
PFS per RECIST 1.1 of ZL-1310 in combination with Atezolizumab up to 24 months Progression free survival (PFS) per RECIST 1.1
PFS per RECIST 1.1 of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months PFS per RECIST 1.1
DCR per RECIST 1.1 of ZL-1310 as a single agent up to 24 months Disease Control Rate (DCR) per RECIST 1.1
DCR per RECIST 1.1 of ZL-1310 in combination with Atezolizumab up to 24 months Disease Control Rate (DCR) per RECIST 1.1
DCR per RECIST 1.1 of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months DCR per RECIST 1.1
Overall Survival of ZL-1310 as a single agent up to 24 months Overall Survival (OS)
Overall Survival of ZL-1310 in combination with Atezolizumab up to 24 months Overall Survival (OS)
Overall Survival of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months Overall Survival (OS)
Pharmacokinetics (PK): Total Antibody of ZL-1310 as a single agent up to 24 months Total Antibody
Pharmacokinetics (PK): Total Antibody of ZL-1310 in combination with Atezolizumab up to 24 months Total Antibody
Pharmacokinetics (PK): Total Antibody of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months Total Antibody
Pharmacokinetics (PK): Unconjugated payloads of ZL-1310 as a single agent up to 24 months Unconjugated payloads
Pharmacokinetics (PK): Unconjugated payloads of ZL-1310 in combination with Atezolizumab up to 24 months Unconjugated payloads
Pharmacokinetics (PK): Unconjugated payloads of ZL-1310 in combination with Atezolizumab and Carboplatin up to 24 months Uncongugated payloads
Trial Locations
- Locations (33)
Zai Lab Site 2030
🇺🇸New Haven, Connecticut, United States
Zai Lab Site 2029
🇺🇸Pittsburgh, Pennsylvania, United States
Zai Lab Site 1004
🇨🇳Hefei, Anhui, China
Zai Lab Site 1012
🇨🇳Xiamen, Fujian, China
Zai Lab Site 1009
🇨🇳Harbin, Heilongjiang, China
Zai Lab Site 1006
🇨🇳Zhengzhou, Henan, China
Zai Lab Site 1014
🇨🇳Changsha, Hunan, China
Zai Lab Site 1016
🇨🇳Nanjing, Jiangsu, China
Zai Lab Site 1008
🇨🇳Ch'ang-ch'un, Jilin, China
Zai Lab Site 1017
🇨🇳Shenyang, Liaoning, China
Zai Lab Site 1015
🇨🇳Xi'an, Shaanxi, China
Zai Lab Site 1011
🇨🇳Jinan, Shandong, China
Zai Lab Site 1010
🇨🇳Shanghai, Shanghai, China
Zai Lab Site 1013
🇨🇳Chengdu, Sichaun, China
Zai Lab Site 2005
🇺🇸Duarte, California, United States
Zai Lab Site 2026
🇺🇸Sarasota, Florida, United States
Zai Lab Site 2013
🇺🇸Detroit, Michigan, United States
Zai Lab Site 2001
🇺🇸Hackensack, New Jersey, United States
Zai Lab Site 2002
🇺🇸Buffalo, New York, United States
Zai Lab Site 2018
🇺🇸Durham, North Carolina, United States
Zai Lab Site 2024
🇺🇸Cleveland, Ohio, United States
Zai Lab Site 2012
🇺🇸Charleston, South Carolina, United States
Zai Lab Site 2006
🇺🇸Fairfax, Virginia, United States
Zai Lab Site 1005
🇨🇳Beijing, Beijing, China
Zai Lab Site 1001
🇨🇳Guangzhou, Guangdong, China
Zai Lab 1002
🇨🇳Wuhan, Hubei, China
Zai Lab Site 1003
🇨🇳Nanchang, Jiangxi, China
Zai Lab Site 8002
🇪🇸Barcelona, Spain
Zai Lab Site 8003
🇪🇸Madrid, Spain
Zai Lab Site 8006
🇪🇸Madrid, Spain
Zai Lab Site 8005
🇪🇸Sevilla, Spain
Zai Lab Site 8004
🇪🇸Valencia, Spain
Zai Lab Site 8001
🇪🇸Valencia, Spain