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临床试验/NCT07681596
NCT07681596招募中1 期

A Modular, Phase I/II, Open-label, Multicentre Study to Evaluate the Safety, Tolerability, Cellular Kinetics, and Efficacy of AZD4045, an Allogeneic Chimeric Antigen Receptor-T Cell (CAR-T) Therapy Targeting B Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma

AstraZeneca24 个研究点 分布在 2 个国家目标入组 101 人开始时间: 2026年7月27日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
招募中
发起方
AstraZeneca
入组人数
101
试验地点
24
主要终点
Adverse events (AEs) and serious AEs (SAEs)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to assess the safety, tolerability, preliminary efficacy, cellular kinetics, and other exploratory endpoints of AZD4045 as a monotherapy and in association with daratumumab and aldesleukin for the treatment of adult participants with RRMM.

详细描述

This modular study aims to evaluate the safety, tolerability, preliminary efficacy, and cellular kinetics of AZD4045 in participants with relapsed or refractory multiple myeloma (RRMM), and determine the recommended Phase 2 dose of AZD4045. Module 1 consists of AZD4045 as a monotherapy and in association with daratumumab and aldesleukin.

研究设计

研究类型
Interventional
分配方式
Non 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 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Participant must be 18 years or older at the time of signing the informed consent form.
  • •Participants must have documented diagnosis of MM according to the IMWG diagnostic criteria.
  • •Participant must have one or more of the following measurable disease criteria:
  • •Serum M-protein level ≥ 1.0 g/dL.
  • •Urine M-protein ≥ 200 mg/24 h.
  • •Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
  • •ECOG performance score of 0 to
  • •Participant must have screening bone marrow aspirate and/or archival sample adequate for clonal sequence calibration for MRD. An archival sample obtained from any time prior is acceptable.
  • •Participant must have adequate organ and bone marrow function.
  • •Participant must have received at least 3 prior classes of therapy, including a PI, an IMiD, and an anti-CD38 antibody
  • •Participant must have documented evidence of PD by IMWG 2016 criteria based on Investigator's determination during or after the most recent line of therapy

排除标准

  • •Participant has a history of any grade IEC-HS and/or history of Grade ≥ 3 CRS and/or Grade ≥ 2 neurotoxicities during prior CAR-T cell therapy or T cell engaging therapy.
  • •Participant has ongoing toxicity from previous anti-cancer therapy that did not resolve to baseline levels or to Grade ≤ 1 with the exception of alopecia or peripheral neuropathy.
  • •Participant has a known active, or prior history of CNS involvement or exhibits clinical signs of meningeal involvement of MM.
  • •Participant has systemic immunoglobulin light chain amyloidosis, active plasma cell leukaemia (presence of ≥ 5% of circulating plasma cells on a conventional peripheral blood smear) at time of screening, Waldenstrom macroglobulinemia or Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin (POEMS) syndrome.
  • •Participant has a history of haematologic malignancies, other than MM, regardless of remission status.
  • •Participant has a history of a prior non-haematologic malignancy unless the participant has been disease-free with no evidence of recurrence for ≥ 2 years.
  • •Participant has significant neurological or psychiatric condition (active or history of).
  • •Participant is positive for any of the following:
  • •HIV (with exceptions)
  • •Chronic or active hepatitis B
  • •Active hepatitis C
  • •Participant has clinically significant cardiovascular disease, including but not limited to:
  • •Myocardial infarction within 6 months prior to eligibility confirmation, or an unstable or uncontrolled disease/condition related to or affecting cardiac function.
  • •Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
  • •Congestive heart failure Class III or IV.
  • •Impaired cardiac function (LVEF < 45%).
  • •Participant has any other significant medical condition which, in the opinion of the Investigator, places the participant at an unacceptable risk for treatment-related complications, could interfere with the successful or safe delivery of therapy, or could interfere with evaluation of study intervention or interpretation of participant safety or study results. These include but are not limited to:
  • •Serious active or uncontrolled infection.
  • •Requirement of supplemental oxygen to maintain oxygen saturation.
  • •Active autoimmune disease or a history of autoimmune disease within 2 years.
  • •Inflammatory bowel disease requiring treatment within the past 5 years or other clinically significant gastrointestinal condition.
  • •Participant received live, attenuated vaccine within 28 days prior to eligibility confirmation
  • •Participant has undergone major surgery within 28 days prior to eligibility confirmation
  • •Concurrent enrolment in another clinical study (unless the study is observational, or the participant is in the follow-up period of an interventional study).
  • •Participant has a known life-threatening allergy, hypersensitivity, intolerance, or a contraindication to any study intervention or their excipients.
  • •Participant received any prior CAR-T or CAR-NK therapy directed at any target within 6 months prior to eligibility confirmation.
  • •Participant received any prior TCE therapy directed at any target within 6 months prior to eligibility confirmation.
  • •Participant received any prior BCMA-targeted treatment within 6 months prior to eligibility confirmation.
  • •Participant with a history of refractoriness to the most recent BCMA-targeted treatment received as defined as PD on or within 60 days of last dose or non-responsiveness (ie, did not achieve at least minimal response) on therapy.
  • •Participant received prior allogeneic stem cell transplant at any time.
  • •Participant received autologous stem cell transplant within 3 months prior to eligibility confirmation.
  • •Participant received radiation therapy for treatment of plasmacytoma within 14 days before eligibility confirmation.
  • •Participant received prior anti-tumour therapy as follows prior to the first dose of lymphodepletion:
  • •a) Within 7 days:
  • •Immunomodulatory or cereblon E3 ligase modulatory drugs. b) Within 14 days:
  • •PI therapy.
  • •Monoclonal antibody treatment for MM.
  • •Cytotoxic therapy.
  • •Other systemic anti-myeloma therapy.
  • •Radiation. c) Within 14 days or at least 5 half-lives, whichever is longer:
  • •Targeted therapy, epigenetic therapy, investigational drug or used an invasive investigational medical device.

研究组 & 干预措施

Module 1: AZD4045 in association with daratumumab and aldesleukin

Experimental

干预措施: Daratumumab (Drug)

Module 1: AZD4045 in association with daratumumab and aldesleukin

Experimental

干预措施: Aldesleukin (Drug)

结局指标

主要结局

Adverse events (AEs) and serious AEs (SAEs)

时间窗: Through study completion, an average of 2 years

Incidence and severity of adverse events (AEs) and serious AEs (SAEs)

Dose-limiting toxicities (DLT)

时间窗: 28 days

Incidence and severity of dose-limiting toxicity (DLT) events

次要结局

  • Efficacy - Objective Response Rate (ORR)(Through study completion, an average of 2 years)
  • Efficacy - Complete Response Rate (CRR)(Through study completion, an average of 2 years)
  • Efficacy - Duration of Response (DOR)(Through study completion, an average of 2 years)
  • Efficacy - Time to Response (TTR)(Through study completion, an average of 2 years)
  • Cellular kinetics - Quantification of CAR transgene levels(Through study completion, an average of 2 years)
  • Cellular kinetics - Tmax(Through study completion, an average of 2 years)
  • Cellular kinetics - Cmax(Through study completion, an average of 2 years)
  • Cellular kinetics - AUC0-28d(0 - 28 days)
  • Cellular kinetics - Tlast(Through study completion, an average of 2 years)
  • Cellular kinetics - Clast(Through study completion, an average of 2 years)
  • Cellular kinetics - AUClast(Through study completion, an average of 2 years)

研究者

发起方
AstraZeneca
申办方类型
Industry
责任方
Sponsor

研究点 (24)

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