A Phase I, Open-label, Multicenter Study of ZL-1218 as a Single Agent and as Combination Therapy With Anti-PD-1 Antibody to Evaluate the Safety, Tolerability, and Pharmacokinetics in Subjects With Advanced Solid Tumor Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 34
- 试验地点
- 15
- 主要终点
- Incidence of Dose Limiting Toxicities
研究概览
简要总结
The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ZL-1218 as a single agent and as combination therapy in subjects with advanced solid tumor malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Adult men and women ≥ 18 years of age. If 18 years is not the age of majority, then adult men and women ≥ age of majority per local regulation.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy > 12 weeks.
- •Subjects must have histologically confirmed and documented diagnosis of locally advanced unresectable or metastatic advanced solid tumor that is refractory to standard treatment, or intolerant to standard treatment, or for which no standard treatment exists.Subjects must have at least one target lesion as defined by RECIST v1.1 on CT, PET/CT, or MRI scan.
- •Subjects must have a site of disease which is not previously irradiated and is safe and amenable to biopsy per the treating institution's guidelines. Subjects must be willing to undergo a tumor biopsy at screening and on treatment, per the protocol guidelines.
- •Subjects must have a site of disease which is not previously irradiated and is safe and amenable to biopsy per the treating institution's guidelines. Subjects must be willing to undergo a tumor biopsy at screening and on treatment, per the protocol guidelines.
排除标准
- •Symptomatic or uncontrolled brain metastasis requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids.
- •Prior exposure to CCR8 inhibitor (anti-CCR8 antibody) or hypersensitivity to any ingredient of the study drug.
- •Out of range value within 10 days prior to the first dose of study treatment.
- •Subjects have received a live or live-attenuated vaccine within 30 days of planned start of study therapy.
- •Subjects with known history of, or any evidence of active, non-infectious pneumonitis.
- •Impaired cardiac function or clinically significant cardiac disease within the last 3 months before administration of the first dose of the study drug.
- •Treatment with any systemic anti-cancer treatment (including investigational products) within 4 weeks before first dose of study drug.
- •Non-palliative radiotherapy within 2 weeks prior to first dose of study drug or have had history of radiation pneumonitis.
- •Major surgery within 4 weeks of the first dose of study drug.
- •Infections requiring systemic antibiotic therapy.
- •Any medical conditions that would, in the investigator's judgement, prevent the subject's participation in the clinical study due to safety concerns, compliance with the study procedures, or interpretation of the study results.
研究组 & 干预措施
Part 1: Dose Escalation; ZL-1218
Drug: ZL-1218 ZL-1218 dose escalation
干预措施: ZL-1218 (Drug)
Part 1: Dose Escalation; ZL-1218 in combination with Pembrolizumab
Drug: ZL-1218 ZL-1218 dose escalation
Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218
干预措施: ZL-1218 (Drug)
Part 1: Dose Escalation; ZL-1218 in combination with Pembrolizumab
Drug: ZL-1218 ZL-1218 dose escalation
Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218
干预措施: Pembrolizumab (Drug)
Part 2: Cohort Expansion; Prior CPI Therapy
Drug: ZL-1218 ZL-1218 recommended dose
Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218
干预措施: ZL-1218 (Drug)
Part 2: Cohort Expansion; Prior CPI Therapy
Drug: ZL-1218 ZL-1218 recommended dose
Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218
干预措施: Pembrolizumab (Drug)
Part 2: Cohort Expansion; CPI therapy Naive
Drug: ZL-1218 ZL-1218 recommended dose
Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218
干预措施: ZL-1218 (Drug)
Part 2: Cohort Expansion; CPI therapy Naive
Drug: ZL-1218 ZL-1218 recommended dose
Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities
时间窗: Approximately 24 months
Number of subjects with dose limiting toxicities (DLTs) through dose escalation only.
Incidence of Treatment Emergent Adverse Events
时间窗: Approximately 24 months
Number of subjects with treatment-emergent adverse effects through dose escalation and expansion.
ORR per RECIST 1.1
时间窗: up to 24 months
Objective Response Rate (ORR) per RECIST 1.1 through dose expansion only.
ORR per iRECIST
时间窗: up to 24 months
Objective Response Rate per iRECIST through dose expansion only.
Clinically Significant changes in safety assessments
时间窗: Approximately 24 months
Changes in safety assessment parameters (e.g., vital signs, electrocardiograms \[ECGs\], and clinical laboratory results) through dose escalation and expansion.
Incidence of Serious adverse events
时间窗: Approximately 24 months
Number of subjects with Serious Adverse Events through dose escalation and expansion.
次要结局
- Pharmacokinetics (PK): AUC(up to 24 months)
- ORR per iRECIST(up to 24 months)
- PFS per iRECIST(up to 24 months)
- Duration of Response per RECIST 1.1(up to 24 months)
- PFS per RECIST 1.1(up to 24 months)
- Pharmacokinetics (PK): Vss(up to 24 months)
- DCR per iRECIST(up to 24 months)
- Duration of Response per iRECIST(up to 24 months)
- Pharmacokinetics (PK): Ctrough(up to 24 months)
- ORR per RECIST 1.1(up to 24 months)
- DCR per RECIST 1.1(up to 24 months)
- Overall Survival(up to 24 months)
- Pharmacokinetics (PK): CL(up to 24 months)
- Pharmacokinetics (PK): t1/2(up to 24 months)
- Pharmacokinetics (PK): Cmax(up to 24 months)
- Pharmacokinetics (PK): Tmax(up to 24 months)
- Immunogenicity(up to 24 months)