2024-516976-14-00已完成2 期
A Phase I/II, Modular, Open-Label, Multi-Centre Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of AZD9750 as Monotherapy and in Combination with Other Anticancer Agents in Participants with Metastatic Prostate Cancer (ANDROMEDA)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 6
- 主要终点
- Part A and B (Safety): Incidence of DLTs (Part A)
研究概览
简要总结
Part A and B: To evaluate the safety and tolerability and determine the MTD and/or the RDE(s)/RP2D of AZD9750 as a monotherapy and in combination with other anticancer agents in participants with mCRPC. Part B only: To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents in participants with mCRPC.
研究设计
- 分配方式
- Na
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥ 18 years at the time of signing the informed consent form.
- •Life expectancy of ≥ 12 weeks.
- •Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
- •Documented metastatic disease by conventional imaging by clear evidence of at least one bone lesion and/or at least one soft tissue lesion.
- •Surgically or medically castrated, with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within (≤) 28 days before first dose of study intervention.
- •Participants who have had disease progression while undergoing continuous ADT following standard treatment of metastatic prostate cancer, per PCWG3 guidance. (a) PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination. (b) Radiographic progression of soft tissue disease by RECIST v1.1 (Eisenhauer et al 2009) with or without PSA progression. (c) Radiographic progression of bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression.
- •ECOG performance status score of 0 or
- •Adequate bone marrow and organ function as defined by the protocol.
- •Participant must be male (as assigned at birth), inclusive of all gender identities.
- •Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
排除标准
- •Participants with pathological finding consistent with any presence of small cell carcinoma, predominant neuroendocrine carcinoma, or any predominant histology other than prostate adenocarcinoma.
- •Brain metastases, or spinal cord compression.
- •Participants with any of the following cardiac criteria: (a) Mean resting QTcF > 450 milliseconds obtained from triplicate ECGs and averaged, recorded within 5 minutes. (b) Any factors that increase the risk of QTc prolongation such as the congenital long QTc syndrome or family history of long QTc syndrome, or unexplained sudden death under 40 years of age in first-degree relatives, or any concomitant medication known to prolong the QTc interval within 5 half-lives of the first dose of study intervention (see Appendix H 1), as well as factors that increase the risk of arrhythmic events such as uncorrected abnormalities in serum electrolytes (ie, sodium, potassium, calcium, magnesium). (c) Resting heart rate > 90 bpm or < 45 bpm. (d) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, or QRS duration > 120 ms, PR interval > 220 ms, second- or third-degree atrioventricular block), and clinically significant sinus node dysfunction not treated with pacemaker. (e) Baseline LVEF < 50%, or clinically significant diastolic dysfunction/LVEDP increase/pulmonary hypertension.
- •Participants with other cardiovascular diseases as defined by any of the following: (a) Symptomatic heart failure (as defined by New York Heart Association class ≥ 2) or recent hospitalisation for heart failure (< 6 months). (b) Uncontrolled hypertension > 160/90 mmHg. (c) Acute coronary syndrome /acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months, symptomatic angina pectoris. (d) Cardiomyopathy of any aetiology. (e) Presence of clinically significant valvular heart disease. (f) History of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (mean HR < 90 bpm over 24 hours or mean HR < 90 bpm on resting ECG) are permitted. (g) Transient ischaemic attack, or stroke within 6 months prior to screening. (h) Participants with symptomatic hypotension at screening.
- •Unresolved treatment-related toxicities from previous anticancer therapy of CTCAE Grade ≥ 2 (with exception of vitiligo, alopecia).
- •Prior treatment with an AR-PROTAC.
研究组 & 干预措施
Saruparib
Test
干预措施: Saruparib (Drug)
AZD9750
Test
干预措施: AZD9750 (Drug)
结局指标
主要结局
Part A and B (Safety): Incidence of DLTs (Part A)
Part A and B (Safety): Incidence of DLTs (Part A)
Part A and B (Safety): Incidence of AEs, SAEs
Part A and B (Safety): Incidence of AEs, SAEs
Part A and B (Safety): AEs leading to discontinuation of study intervention
Part A and B (Safety): AEs leading to discontinuation of study intervention
Part A and B (Safety): Clinically significant changes from baseline in vital signs, physical examination, ECOG PS, ECGs and laboratory parameters.
Part A and B (Safety): Clinically significant changes from baseline in vital signs, physical examination, ECOG PS, ECGs and laboratory parameters.
Part B only (Efficacy): Proportion of participants achieving a ≥ 50% decrease in PSA from baseline.
Part B only (Efficacy): Proportion of participants achieving a ≥ 50% decrease in PSA from baseline.
次要结局
- For Part A and B (Efficacy): Proportion of participants achieving a ≥ 50% decrease in PSA from baseline (Part A).
- For Part A and B (Efficacy): Proportion of participants achieving a ≥ 90% decrease in PSA from baseline.
- For Part A and B (Efficacy): ORR, DoR, TTR, rPFS assessed by the Investigator according to RECIST v1.1 (soft tissue) and PCWG3 (bone) criteria.
- For Part A and B (Efficacy): Best percentage change in TL size from baseline using RECIST v1.1.
- For Part A and B (Efficacy): Time to PSA response and Time to PSA progression according to PCWG3 criteria.
- For Part A and B (PK): Plasma concentrations and PK parameters including, but not limited to Cmax, tmax and AUC after oral administration of AZD9750, if data allows.
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (6)
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