An Open-label, Multi-drug, Multi-center Phase II Combination Study of AZD4635 in Patients With Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Confirmed Objective Response Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
研究概览
简要总结
This is an open-label Phase II modular study in participants with prostate cancer which will assess safety, efficacy, and tolerability of AZD4635 in combination with other therapeutic agents in different treatment arms (referred to as modules).
Combinations to be studied include: 1) Module 1: AZD4635 plus durvalumab; 2) Module 2: AZD4635 plus oleclumab.
详细描述
This is an open-label Phase II modular study in participants with prostate cancer which will assess safety, efficacy, and tolerability of AZD4635 in combination with other therapeutic agents in different treatment arm (referred to as modules).
Combinations to be studied include: 1) Module 1: AZD4635 plus durvalumab; 2) Module 2: AZD4635 plus oleclumab.
All participants will be allocated into a module using an Interactive Web Response System (IWRS). Randomization will occur when patients meet eligibility criteria for two or more modules that are currently recruiting. If participants only meet the criteria for one currently recruiting module, they will be allocated to that module without randomization taking place.
The primary objective of the clinical study is to evaluate the efficacy of each combination therapy by: 1) assessing the objective response rate (ORR) of participants with measurable disease (response will be determined by Response Evaluation Criteria in Solid Tumours [RECIST 1.1]); 2) assessing the prostate-specific antiget (PSA) confirmed response rate of each combination therapy (PSA confirmed response rate is defined as the proportion of participants with a reduction in the PSA level of ≥50% measured from baseline to the lowest post-baseline PSA result measured twice, at least 3 weeks apart by the Prostate Cancer Working Group 3 criteria [PCWG3]).
The safety endpoints include assessment of adverse events and serious adverse events, physical examinations, vital signs, and collection of clinical chemistry/hematology parameters
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 130 Years（Adult, Older Adult）
- 性别
- Male
- 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
Module 1 (AZD4635 75 mg + Durvalumab 1500 mg)
Participants will receive monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter will continue to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until will derive clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.
干预措施: AZD4635 (Drug)
Module 1 (AZD4635 75 mg + Durvalumab 1500 mg)
Participants will receive monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter will continue to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until will derive clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.
干预措施: Durvalumab (Drug)
Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Participants will receive combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.
干预措施: AZD4635 (Drug)
Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Participants will receive combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.
干预措施: Oleclumab (Drug)
结局指标
主要结局
Percentage of Participants With Confirmed Objective Response Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months)
The confirmed objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines, assessed by computed tomography (CT) scan/ magnetic resonance imaging (MRI) scan/ positron emission tomography (PET) scan and bone scan. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.
Percentage of Participants With Confirmed Prostate-specific Antigen (PSA) Response Per Prostate Cancer Working Group 3 (PCWG3) Criteria
时间窗: Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months)
A confirmed PSA response is defined as reduction in the PSA level of \>= 50% from baseline to the lowest post-baseline PSA results, measured twice, at least 3 weeks apart by the PCWG3 criteria.
次要结局
- Percentage of Participants With Radiological Progression Free Survival (rPFS) at 6 Months(Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months))
- Duration of Response (DoR)(Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months))
- Overall Survival (OS)(Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months))
- Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab(Pre-dose on Day 1 of Cycles 1, 2, 4, and 7 and 90 days following the last dose of durvalumab (approximately 22 months))
- Number of Participants With Positive ADA to Oleclumab(Pre-dose on Day 1 of Cycles 1, 3, 5, and every 12 weeks thereafter, and 90 days following the last dose of oleclumab (approximately 22 months))
- Plasma Concentrations of AZD4635 and Its Metabolites (SSP-005173 and SSP-005174)(Predose on Day 1 of Cycle 7)
- Plasma Concentration of Durvalumab(Predose and end of infusion on Day 1 of Cycle 7)
- Plasma Concentration of Oleclumab(Predose and 10 minutes end of infusion on Day 1 of Cycle 14)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(Day 1 through 90 days after the last dose of study drug (approximately 22 months))
- Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs(Day 1 through 90 days after the last dose of study drug (approximately 22 months))
- Number of Participants With Common Terminology Criteria for Adverse Events (CTCAE) Grade Change in Laboratory Parameters From Baseline to Grade 3 or More(Baseline (Day 1) through 90 days after the last dose of study drug (approximately 22 months))