2023-506747-42-00招募中2 期
PRIMAVERA: A Modular Phase I/II, Open-label, Multicentre Study to Evaluate the Safety,Tolerability, and Efficacy of AZD3470, a PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agent(s) in Participants With Relapsed/Refractory Haematologic Malignancies
Astrazeneca AB, Astrazeneca AB10 个研究点 分布在 4 个国家目标入组 50 人开始时间: 2024年3月27日最近更新:
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 10
- 主要终点
- Incidence and severity of AEs and SAEs- Occurrence of DLTs (dose escalation)
研究概览
简要总结
To assess the safety and tolerability and determine RP2D of AZD3470 as monotherapy and in combination with other anticancer agents in participants with r/r haematological malignancies.
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •In Part A (dose escalation), participants must be aged ≥ 18 years at the time of signing the informed consent. In Part B (dose optimization/expansion), participants must be at least 15 years of age
- •Histologically confirmed documented diagnosis of r/r cHL based on criteria established by the World Health Organization
- •Willing to provide FFPE baseline tumour tissue to meet the minimum tissue requirementfor central MTAP expression determination.
- •Participants must have documented r/r active disease, must have previously received atleast 3 prior lines of therapy (including Brentuximab Vedotin and anti-PD-1therapy) for the treatment of cHL, and must have exhausted allavailable therapies with demonstrated clinical benefit. A prior line of therapy is consideredas a minimum of 2 complete cycles.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Module 1 (cHL)
- •Module 1: - At least 1 radiographically measurable, and/or FDG-avid lymphoma lesion > 1.5 cm. - Adequate organ and bone marrow function - Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
排除标准
- •Any significant laboratory finding or any severe and uncontrolled medical condition
- •Any of the following cardiac criteria: o Mean resting QTcF > 470 msec or clinically important abnormalities in rhythm (ventricular arrhythmias and uncontrolled atrial fibrillation) o Factors that increase the risk of QTc prolongation or risk of arrhythmic events o Cardiac procedures or conditions within the last 6 months: Coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) or heart valve intervention vascular stentimplantation, acute coronary syndrome / myocardial infarction, uncontrolled anginapectoris, use of therapeutic anti-coagulation for treatment of active thromboembolic events. o Severe valvular heart disease o Congestive heart failure Grade II to Grade IV o Prior or current cardiomyopathy o Uncontrolled hypertension o Brain perfusion problems such as haemorrhagic or thrombotic stroke (including transient ischemic attacks)
- •Unresolved non-haematological toxicity from prior anticancer therapy of Grade > 1, except alopecia.
- •History of another primary malignancy.
- •History of significant haemoptysis or haemorrhage within 4 weeks of the first dose of study treatment.
- •Requires ongoing immunosuppressive therapy, including systemic corticosteroids.
- •Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
- •Active CNS involvement by lymphoma, leptomeningeal disease, or spinal cord compression.
- •Serologic active HBV or HCV infection.
- •Known to have tested positive for HIV.
- •Active gastrointestinal disease or other condition that will interfere with oral therapy.
结局指标
主要结局
Incidence and severity of AEs and SAEs- Occurrence of DLTs (dose escalation)
Incidence and severity of AEs and SAEs- Occurrence of DLTs (dose escalation)
次要结局
- Radiological response assessed by the Investigator evaluated according to the LuganoClassification for cHL
- Objective response rate (ORR) - The proportion of patients with an investigator assessedcomplete or partial response
- Complete response rate (CRR) – The proportion of patients with an investigator assessedcomplete response
- Duration of response (DoR) - the time from date of first documented objective responseuntil date of documented disease progression per Lugano classification as assessed by theinvestigator or death due to any cause.
- Progression Free Survival (PFS) - defined as time from date of first dose (nonrandomisedstudy parts) or date of randomisation (randomised study parts) until progression perLugano classification as assessed by the Investigator, or death due to any cause.
- Overall Survival (OS) - defined as time from date of first dose (nonrandomised studyparts) or date of randomisation (randomised study parts) until the date of death due to any cause.
- Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: Area under the concentration time curve (AUC), maximumobserved plasma concentration of the study drug (C-max), Time to maximum observed plasma concentration of the study drug (T-max), amount of AZD3470 excreted in urine (Ae), renalclearance (Clr).
- Part B (Dose expansion) - Measurement of PK parameters: Area under the concentration time curve (AUC),maximum observed plasma concentration of the study drug (C-max), Time to maximumobserved plasma concentration of the study drug (T-max) - Plasma geometric mean ratio (Cmax and AUC) of AZD3470 evaluated with and withoutfood
研究者
Michelle Beharry
Scientific
Astrazeneca AB
研究点 (10)
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