An Open-label, Multicenter Study of ZL-1310 to Evaluate the Safety, Efficacy, and Pharmacokinetics in Participants With Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 339
- 试验地点
- 98
- 主要终点
- 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)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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:
- •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.
- •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.
研究组 & 干预措施
Dose Escalation: Part 1C
ZL-1310 in combination with Atezolizumab and Carboplatin as induction and followed by ZL-1310 and Atezolizumab as maintenance
干预措施: Atezolizumab (Drug)
Dose Escalation: Part 1C
ZL-1310 in combination with Atezolizumab and Carboplatin as induction and followed by ZL-1310 and Atezolizumab as maintenance
干预措施: ZL-1310 (Drug)
Dose Expansion: Part 1B
ZL-1310 in combination with Atezolizumab
干预措施: Atezolizumab (Drug)
Dose Escalation: Part 1A
ZL-1310 as a single-agent
干预措施: ZL-1310 (Drug)
Dose Expansion: Part 1B
ZL-1310 in combination with Atezolizumab
干预措施: ZL-1310 (Drug)
Doublet Dose Optimization: Arm 1 (Part 3)
Dose level 1 of ZL-1310 established from single agent dose escalation, in combination with Atezolizumab
干预措施: ZL-1310 (Drug)
Doublet Dose Optimization: Arm 1 (Part 3)
Dose level 1 of ZL-1310 established from single agent dose escalation, in combination with Atezolizumab
干预措施: Atezolizumab (Drug)
Doublet Dose Optimization: Arm 2 (Part 3)
Dose level 2 of ZL-1310 established from single agent dose escalation in combination with Atezolizumab
干预措施: ZL-1310 (Drug)
Doublet Dose Optimization: Arm 2 (Part 3)
Dose level 2 of ZL-1310 established from single agent dose escalation in combination with Atezolizumab
干预措施: Atezolizumab (Drug)
Triplet Dose Optimization: Arm 1 (Part 4)
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
干预措施: ZL-1310 (Drug)
Triplet Dose Optimization: Arm 1 (Part 4)
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
干预措施: Atezolizumab (Drug)
Triplet Dose Optimization: Arm 1 (Part 4)
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
干预措施: Carboplatin (Drug)
Triplet Dose Optimization: Arm 2 (Part 4)
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
干预措施: ZL-1310 (Drug)
Triplet Dose Optimization: Arm 2 (Part 4)
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
干预措施: Atezolizumab (Drug)
Triplet Dose Optimization: Arm 2 (Part 4)
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
干预措施: Carboplatin (Drug)
Dose Expansion: Arm 2 (Part 2)
Dose level 2 of ZL-1310 established from single-agent dose escalation
干预措施: ZL-1310 (Drug)
Dose Extension: Arm 1 (Part 2)
ZL-1310 as a single agent
干预措施: ZL-1310 (Drug)
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.
干预措施: ZL-1310 (Drug)
Doublet Dose Optimization: Arm 2 (Part 3A)
Dose level 2 of ZL-1310 established from single agent dose escalation in combination with Atezolizumab
干预措施: Atezolizumab (Drug)
Dose Escalation: Part 1C
ZL-1310 in combination with Atezolizumab and Carboplatin as induction and followed by ZL-1310 and Atezolizumab as maintenance
干预措施: Carboplatin (Drug)
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.
干预措施: ZL-1310 (Drug)
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
干预措施: ZL-1310 (Drug)
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.
干预措施: Carboplatin (Drug)
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
干预措施: Carboplatin (Drug)
Doublet Dose Optimization: Arm 1 (Part 3A)
Dose level 1 of ZL-1310 established from single agent dose escalation, in combination with Atezolizumab
干预措施: Atezolizumab (Drug)
Doublet Dose Optimization: Arm 2 (Part 3A)
Dose level 2 of ZL-1310 established from single agent dose escalation in combination with Atezolizumab
干预措施: ZL-1310 (Drug)
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
干预措施: ZL-1310 (Drug)
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.
干预措施: Atezolizumab (Drug)
Dose Expansion: Arm 1 (Part 2)
Dose level 1 of ZL-1310 established from single-agent dose-escalation
干预措施: ZL-1310 (Drug)
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.
干预措施: Atezolizumab (Drug)
Doublet Dose Optimization: Arm 1 (Part 3A)
Dose level 1 of ZL-1310 established from single agent dose escalation, in combination with Atezolizumab
干预措施: ZL-1310 (Drug)
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
干预措施: Atezolizumab (Drug)
Dose Extension: Part 2-1
single-agent dose extension for Post-anti-DLL3
干预措施: ZL-1310 (Drug)
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
干预措施: Carboplatin (Drug)
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
干预措施: Atezolizumab (Drug)
结局指标
主要结局
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)
时间窗: 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 (Part 1A), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C)
时间窗: 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 (Part 1A), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C)
时间窗: up to 24 months
Number of subjects with serious adverse events
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)
时间窗: up to 24 months
Number of subjects with treatment emergent adverse events leading to dose modifications and/or study treatment discontinuation
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)
时间窗: up to 24 months
Number of subjects with serious adverse events
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)
时间窗: up to 24 months
antitumor activity per RECIST v1.1 by investigator's assessment
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)
时间窗: up to 24 months
objective response rate per RECIST v1.1
Disease control rate (DCR) per RECIST v1.1 of ZL-1310 in combination with atezolizumab
时间窗: up to 24 months
disease control rate per RECIST v1.1
次要结局
- 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)(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)(up to 24 months)
- Duration of response per RECIST v1.1(up to 24 months)
- Progression free survival per RECIST v1.1(up to 24 months)
- Overall Survival of ZL-1310(up to 24 months)
- Pharmacokinetics: Total Antibody of ZL-1310(up to 24 months)
- Pharmacokinetics: Unconjugated payloads of ZL-1310(up to 24 months)