Phase I/II Dose Escalation & Dose Optimization Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD8359, a CD8-guided T Cell-engaging Antibody That Targets STEAP2, in Adult Participants With Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 42
- 试验地点
- 10
- 主要终点
- Number of participants with adverse events (AE), adverse events of special interest (AESI), and serious adverse events (SAE)
研究概览
简要总结
This study is being conducted to learn more about the safety, tolerability, and effectiveness of an experimental treatment for metastatic prostate cancer called AZD8359. The study is split into different modules which will look at AZD8359 delivered by different methods. The study is also further split into 2 parts, Part A which will test different dose levels and dosing schedules of AZD8359 to determine which doses are the best in terms of safety and side effects (dose escalation), and Part B will further test at least two AZD8359 doses in a larger group of participants (dose expansion).
详细描述
This is a first-in-human, modular, Phase I/II, open label, multicenter study of AZD8359, in adult participants with metastatic prostate cancer. The study will consist of study modules, each evaluating the the safety, tolerability, preliminary efficacy, immune cell activation and anti-tumor activity of AZD8359. The study will also characterize the pharmacokinetics and immunogenicity of AZD8359.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 100 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer
- •Surgically or medically castrated with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L)
- •PSA value at screening should be ≥ 1ng/mL
- •Evidence of disease progression within 6 months prior to screening
- •Part A Participants should have received at least 2 prior approved systemic therapies for prostate cancer with at least one androgen receptor pathway inhibitor and at least one taxane regimen if amenable
- •Part B Participants should have received an androgen receptor pathway inhibitor for metastatic hormone sensitive prostate cancer or metastatic castration resistant prostate cancer (mCRPC). No prior taxane treatment for mCRPC is allowed for Module 1 and 2 Part B patients
- •Adequate organ function
- •Body weight ≥ 35 kg
排除标准
- •Any clinically relevant cardiac abnormalities such as QT prolongation or uncontrolled cardiac arrythmias
- •All prior treatment-related adverse events must have resolved to Grade ≤ 2
- •History of Grade ≥ 3 cytokine release syndrome or Grade ≥ 2 immune effector cell-associated neurotoxicity syndrome with prior therapy
- •Active or prior documented autoimmune or inflammatory disorders within the past 3 years
- •Prior exposure to any STEAP2 targeted agents or TCEs for prostate cancer
研究组 & 干预措施
Module 1 - Part A (Dose Escalation)
干预措施: AZD8359 (Drug)
Module 1/2 - Part B2 (Dose Expansion)
干预措施: AZD8359 (Drug)
Module 2 - Part A (Dose Escalation)
干预措施: AZD8359 (Drug)
Module 1/2 - Part B1 (Dose Expansion)
干预措施: AZD8359 (Drug)
结局指标
主要结局
Number of participants with adverse events (AE), adverse events of special interest (AESI), and serious adverse events (SAE)
时间窗: From time of Informed Consent to 90 days post last dose of study intervention (up to 3 years)
Number of participants with AEs, AESIs, SAEs, including AEs leading to discontinuation of study intervention and clinically significant alterations from baseline in laboratory parameters, vital signs, ECGs and physical examination results
Number of participants with dose-limiting toxicity (DLT), as defined in the protocol (Part A only)
时间窗: From first study dose to 21 OR 28 days post first dose based on schedule
A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness
PSA response rate (Part B only)
时间窗: Up to 3 years
Number of participants with a PSA50 response
次要结局
- PSA Response rate (Part A only)(Up to 3 years)
- PSA Response rate(Up to 3 years)
- Time to PSA response(Up to 3 years)
- Duration of PSA response(Up to 3 years)
- Durable PSA response rate(Up to 3 years)
- Time to PSA progression(Up to 3 years)
- Objective Response Rate (ORR)(Up to 3 years)
- Duration of Response (DoR)(Up to 3 years)
- Disease Control Rate (DCR)(16 Weeks)
- Time To Response (TTR)(Up to 3 years)
- Radiographic Progression Free Survival (rPFS)(Up to 3 years)
- Durable Response Rate (DRR)(Up to 3 years)
- Target Lesion Percentage change(Up to 3 years)
- Overall Survival (OS) 12 months(12 months)
- Overall Survival (OS)(Up to 3 years)
- Symptomatic Skeletal Related Events (SSRE)(Up to 3 years)
- Serum Concentration of AZD8359(From first dose through Day 28 after the last study-drug dose, at predefined intervals)
- Pharmacokinetics of AZD8359 (Cmax)(From first dose through Day 28 after the last study-drug dose, at predefined intervals)
- Pharmacokinetics of AZD8359 (AUC)(From first dose through Day 28 after the last study-drug dose, at predefined intervals)
- Pharmacokinetics of AZD8359 (Tmax)(From first dose through Day 28 after the last study-drug dose, at predefined intervals)
- Pharmacokinetics of AZD8359 (Clerance)(From first dose through Day 28 after the last study-drug dose, at predefined intervals)
- Pharmacokinetics of AZD8359 (t1/2)(From first dose through Day 28 after the last study-drug dose, at predefined intervals)
- Immunogenicity of AZD8359 (ADA)(From first dose through Day 28 after the last study-drug dose, at predefined intervals)
- Tumor STEAP2 expression(Up to 3 years)