2023-506757-38-00招募中1 期
PRIMROSE: A Modular Phase I/IIa, Multi-centre, Dose Escalation, and Expansion Study of AZD3470, a MTA Cooperative PRMT5 Inhibitor, as Monotherapy and in Combination with Anticancer Agents in Patients with Advanced/Metastatic Solid Tumours That are MTAP Deficient
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 5
- 主要终点
- Incidence of adverse events (AEs) determined by the number of patients with adverse events by system organ class and preferred term.
研究概览
简要总结
To assess the safety and tolerability, and to determine the RP2D of AZD3470 as monotherapy and in combination with anti-cancer agents in participants with MTAP deficient advanced solid tumors.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Participant must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the ICF.
- •Willing to provide archival and/or baseline tumor sample to meet the minimum tissue requirement for central MTAP deficiency testing.
- •Participants must have received and progressed, are refractory or are intolerant to standard therapy for the specific tumor type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting.
- •MTAP deficient tumors defined as evidence of homozygous deletion of one or more exons of the MTAP gene in tumor tissue AND/OR loss of MTAP expression in the tumor tissue.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •A minimum life expectance of 12 weeks in the opinion of the Investigator.
- •Participants must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Adequate organ and bone marrow reserve function.
- •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
- •Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease or primary malignancies of the central nervous system. - Allogeneic organ transplantation. - Any significant laboratory finding or any severe and uncontrolled medical condition - Any of the following cardiac criteria: - LVEF ≤ 50%, prior or current cardiomyopathy - clinically active cardiovascular disease, or a history of myocardial infarction within the last 6 months - uncontrolled Angina or acute coronary syndrome within 6 months - severe valvular heart disease - uncontrolled hypertension - risk of brain perfusion problems, stroke or transient ischemic attack in the last 6 months, undergone coronary artery bypass graft, angioplasty or vascular stent - chronic heart failure - factors that increase the risk of QTc prolongation or risk of arrhythmic events - Mean resting QTcF > 470 msec or any clinically important abnormalities in rhythm
- •Use of therapeutic anti-coagulation for treatment of acute thromboembolic events. - Serologic active hepatitis B or C infection. - Known to have tested positive for Human immunodeficiency virus (HIV). - Confirmed or suspected ILD/pneumonitis or history of (non-infectious) ILD/pneumonitis that required oral or IV steroids or supplemental oxygen - Active gastrointestinal disease or other condition that would interfere with oral therapy. - History of another primary malignancy. - Unresolved toxicities from prior anti-cancer therapy, except alopecia and neuropathy. - Prior treatment with a protein arginine methyltransferase 5 (PRMT5) inhibitor.
研究组 & 干预措施
Midazolam-ratiopharm® 2 mg/ml orale Lösung, AZD3470, DEXTROMETHORPHANE ELERTE 1,5 mg/ml, sirop, AZD3470
Test
干预措施: Midazolam-ratiopharm® 2 mg/ml orale Lösung (Drug)
Midazolam-ratiopharm® 2 mg/ml orale Lösung, AZD3470, DEXTROMETHORPHANE ELERTE 1,5 mg/ml, sirop, AZD3470
Test
干预措施: AZD3470 (Drug)
Midazolam-ratiopharm® 2 mg/ml orale Lösung, AZD3470, DEXTROMETHORPHANE ELERTE 1,5 mg/ml, sirop, AZD3470
Test
干预措施: DEXTROMETHORPHANE ELERTE 1,5 mg/ml, sirop (Drug)
结局指标
主要结局
Incidence of adverse events (AEs) determined by the number of patients with adverse events by system organ class and preferred term.
Incidence of adverse events (AEs) determined by the number of patients with adverse events by system organ class and preferred term.
Incidence of serious adverse events (SAEs) determined by the number of patients with adverse events by system organ class and preferred term.
Incidence of serious adverse events (SAEs) determined by the number of patients with adverse events by system organ class and preferred term.
Incidence of dose-limiting toxicities (DLT) as determined by number of patients with at least 1 dose-limiting toxicity (DLT) as defined by the clinical study protocol
Incidence of dose-limiting toxicities (DLT) as determined by number of patients with at least 1 dose-limiting toxicity (DLT) as defined by the clinical study protocol
次要结局
- Radiological response assessed by the Investigator evaluated according to RECIST v1.1 1. Objective response rate (ORR) - The percentage or number of participants who have a confirmed investigator assessed complete or partial response as determined by the investigator according to response criteria in solid tumors (RECIST v1.1).
- Duration of response (DOR) - the time from date of first documented objective response (which is subsequently confirmed) until date of documented disease progression per Tumor RECIST v1.1 as assessed by the Investigator at local site or death due to any cause.
- Disease Control Rate (DCR) at 12 weeks- defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST 1.1 as assessed by the Investigator at local site and derived from the raw tumor data for at least 11 weeks after date of first dose to allow for an early assessment within the assessment window.
- Best percentage change in tumor size - Percentage change from baseline in TL (target lesion) tumor-size is based on the RECIST 1.1 TL measurements as assessed by the Investigator.
- Progression Free Survival (PFS) - defined as time from date of first dose (nonrandomized study parts) or date of randomization (randomized study parts) until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause.
- Overall Survival (OS) - defined as time from date of first dose (nonrandomized study parts) or date of randomization (randomized 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), maximum observed plasma concentration of the study drug (Cmax), Time to maximum observed plasma concentration of the study drug (T-max), Terminal elimination half-life (t 1/2), amount of AZD3470 excreted in urine (Ae), renal clearance (Clr)
- (USA ONLY) Module 1 Endpoints Part A (DDI) - Plasma geometric mean ratio (Cmax and AUC) of Midazolam evaluated with and without AZD3470 - Plasma geometric mean ratio (Cmax and AUC) of Dextromethorphan evaluated with and without AZD3470 - Percentage change from baseline tumor SDMA as measured by immunohistochemistry.
研究者
Clinical Study Information Centre
Scientific
Astrazeneca AB
研究点 (5)
Loading locations...
相似试验
招募中
2 期
A trial to learn how safe AZD3632 is, how well it works, and how it moves throughout the body over time in adults with acute leukemia and myelodysplastic syndrome with HOX gene overexpression2025-521299-76-00AstraZeneca AB1
招募中
2 期
A trial to learn how safe AZD4512 is and how it works in the bodies of people with B-cell acute lymphoblastic leukemia (B-ALL)2025-522372-93-00AstraZeneca AB13
招募中
1 期
A Trial to Learn How Safe AZD9750 is and How Well it Works in People With Metastatic Prostate Cancer When Given With or Without Other Anticancer DrugsProstate CancerNCT07336446AstraZeneca300
招募中
2 期
Phase 2 Study of ZN‑c3 in High-Grade Serous Ovarian Cancer2022-502983-19-00K-Group Beta Inc.194
招募中
1 期
A Study to Investigate Safety, Tolerability, and Pharmacokinetics of AZD3974 in Healthy ParticipantsNCT07290283AstraZeneca176