A Phase I/IIa First-in-human, Open-label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of AZD8853 in Participants With Selected Advanced/Metastatic Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
A Phase I/IIa First-in-human, Open-label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of AZD8853 in Participants with Selected Advanced/Metastatic Solid Tumours.
详细描述
This study is evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AZD8853 in participants with advanced, unresectable or metastatic Non-Small Cell Lung Cancer (NSCLC), Microsatellite Stable Colorectal Cancer (MSS-CRC), Urothelial Carcinoma (UC).
This is a modular study, that includes a master protocol and Substudies.
Substudy 1 will be conducted in 3 parts - Part A: Dose escalation, Part B: Safety expansion and exploratory CD8+ T cell radiopharmaceutical tracer with PET imaging, and Part C: Efficacy expansion.
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Substudy 1 - Parts A, B, and C
- Part A: AZD8853 monotherapy dose escalation
- Part B1 and Part B2: AZD8853 monotherapy safety expansion at dose levels and indications determined to be safe in Part A
- Part C1 and Part C2: AZD8853 monotherapy safety and preliminary efficacy expansion at dose levels and indications determined to be safe in Parts A and B
干预措施: AZD8853 (Drug)
Substudy 1 - Parts B1 and B2 with CD8+ PET
Sub-set of participants from Parts B1 and B2 will also receive investigational CD8+ T cell targeted radioactive tracer, Zirconium-89 crefmirlimab berdoxam with PET scans
干预措施: Zirconium-89 crefmirlimab berdoxam (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)
The safety and tolerability of AZD8853 in participants with selected advanced/metastatic solid tumors was assessed. As per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, severity scale ranged from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. This outcome measure was assessed only for substudy 1 Part A.
Number of Participants With Dose Limiting Toxicity (DLT)
时间窗: From Cycle 1 Day 1 to end of Cycle 1 (21 days)
DLTs (in dose escalation Parts only) of AZD8853 in participants with selected advanced/metastatic solid tumors was assessed. The DLTs are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) as per NCI-CTCAE version 5.0 non-hematological toxicity or hematological toxicity. This outcome measure was assessed only for substudy 1 Part A.
次要结局
- Objective Response Rate (ORR)(First dose until progression of disease (PD) or last evaluable assessment in the absence of progression (1 Year))
- Disease Control Rate (DCR) at 15 Weeks(15 weeks)
- Duration of Response (DOR)(First documented response until date of first documented disease progression or study end (1 Year))
- Progression Free Survival (PFS)(First dose until documented disease progression or study end (1 Year))
- Percentage Change From Baseline in Tumor Size(Baseline (pre-treatment) up to Week 6 and Week 15)
- Overall Survival (OS)(First dose until study end (1 Year))
- Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline(Baseline (pre-treatment), Day 8 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3, 4, 5, 7 (each cycle is equal to 21 days))
- Maximum Observed Concentration (Cmax) of AZD8853(0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days))
- Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853(0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days))
- Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853(0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days))
- Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels(0 hours post EOI of Cycle 1 Day 1, Day 1 (Pre-dose) of Cycles 2 and 3 (each cycle equals to 21 days) and 90-days post EOT of 90 days follow-up)
- Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853(0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days))
- Number of Participants With Positive Anti-drug Antibody (ADA) of AZD8853(From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 year))