A Phase Ib/II Study of AZD0120, Dual-Targeting Autologous Chimeric Antigen Receptor T-cell (CAR T) Therapy Directed Against CD19 and B-cell Maturation Antigen (BCMA) in Participants With Relapsed/Refractory Multiple Myeloma (DURGA-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 232
- 试验地点
- 37
- 主要终点
- Phase 1b: Adverse Events (AEs)
研究概览
简要总结
This trial is a Phase 1b/2, open-label, multicenter study of AZD0120, a CD19/BCMA dual CAR T-cell therapy, in adult subjects with relapsed/refractory multiple myeloma.
详细描述
Phase 1b aims to evaluate the safety, tolerability, pharmacokinetic characteristics, pharmacodynamic effect, and immunogenicity in subjects with relapsed/refractory multiple myeloma and determine the recommended Phase 2 dose of AZD0120.
Phase II aims to evaluate the efficacy of AZD0120, and to further characterize the safety, pharmacodynamic effects, immunogenicity, and changes in health-related quality of life parameters in subjects with relapsed/refractory multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •≥18 years of age at the time of consent.
- •ECOG performance status of 0 or
- •Documented diagnosis of MM per IMWG diagnostic criteria.
- •Participant must have received at least 3 prior lines of therapy, which include a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody.
- •Have documented evidence of progressive disease per IMWG criteria.
- •Participant must have measurable disease at screening.
- •Participant must have adequate bone marrow and organ function (hematological, hepatic and renal) demonstrated at screening.
排除标准
- •Participant has a history of significant toxicity during prior CAR T-cell therapy and T-cell engaging therapy.
- •Participant has a history of a prior non-hematologic malignancy, unless the participant has been disease-free with no evidence of recurrence for ≥ 2 years. Some exceptions may apply.
- •Participant has significant cardiac, neurological, or psychiatric conditions.
- •Any other significant medical conditions such as:
- •Serious active or uncontrolled infection
- •Active autoimmune disease or a history of autoimmune disease within 2 years
- •Active plasma cell leukemia at the time of screening
- •Clinical evidence of dementia or altered mental status, or stroke, intracranial haemorrhage, or seizure within 6 months before signing informed consent form (ICF).
- •Known active or prior history of central nervous system involvement or exhibits clinical signs of meningeal involvement of MM.
- •Other protocol-defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
AZD0120
AZD0120 will be administered by infusion
干预措施: AZD0120 (Biological)
结局指标
主要结局
Phase 1b: Adverse Events (AEs)
时间窗: Through study completion, a minimum of 2 years.
The incidence and severity of AEs.
Phase 1b: Dose-Limiting Toxicities (DLTs)
时间窗: 28 days
The DLT evaluation period is defined as the first 28 days after infusion.
Phase 2: Objective Response Rate (ORR)
时间窗: Through study completion, a minimum of 2 years.
Defined as the proportion of participants who achieved partial response (PR) or better by the International Myeloma Working Group (IMWG) response criteria.
Phase 1b Dose-limiting toxicities
时间窗: 28 days
The DLT evaluation period is defined as the first 28 days of Cycle 1
Phase 2 Overall response rate (ORR)
时间窗: 2 years
Overall response rate (ORR) as defined by the International Myeloma Working Group (IMWG)
Phase 1b Adverse Events (AEs)
时间窗: 2 years
The incidence and severity of adverse events (AEs)
次要结局
- Phase 1b and 2: Complete response rate (CRR)(Through study completion, a minimum of 2 years.)
- Phase 1b: Objective Response Rate (ORR)(Through study completion, a minimum of 2 years.)
- Phase 1b and 2: Minimal Residual Disease (MRD) negative Complete Response (CR) rate(Through study completion, a minimum of 2 years.)
- Phase 1b and 2: Minimal Residual Disease (MRD) negative rate at 12 months(12 months)
- Phase 1b and 2: Duration of response (DOR)(Through study completion, a minimum of 2 years.)
- Phase 2: Adverse Events (AEs)(Through study completion, a minimum of 2 years.)
- Ph1b and 2: Pharmacokinetics - AUC(Through study completion, a minimum of 2 years.)
- Ph1b and 2: Pharmacokinetics - Clast(Through study completion, a minimum of 2 years.)
- Ph1b and 2: Pharmacokinetics - Cmax(Through study completion, a minimum of 2 years.)
- Ph1b and 2: Pharmacokinetics - Tlast(Through study completion, a minimum of 2 years.)
- Ph1b and 2: Pharmacokinetics - Tmax(Through study completion, a minimum of 2 years)
- Phase 1b: Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM 2021)(Through study completion, a minimum of 2 years.)
- Phase 1b: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 2021)(Through study completion, a minimum of 2 years.)
- Phase 1b: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma-20 (EORTC QLQ-MY20 2021)(Through study completion, a minimum of 2 years.)
- Phase 2: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire IL355 (EORTC IL355)(Through study completion, a minimum of 2 years.)
- Phase 2: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC IL356(Through study completion, a minimum of 2 years.)
- Phase 1b Pharmacokinetic - AUC(2 years)
- Phase 1b Pharmacokinetic - Cmax(2 years)
- Phase 1b Pharmacokinetic - half-life(2 years)
- Phase 1b Pharmacokinetic - Tmax(2 years)
- Phase 2: Adverse Events (AEs)(2 years)
- Phase 1b and 2: Overall Response Rate (ORR)(2 years)
- Phase 1b and 2: MRD negative rate(2 years)
- Phase 1b and 2: Duration of response (DOR)(2 years)
- Phase 1b and 2: PFS(2 years)
- Phase 1b and 2: OS(2 years)
- Phase 1b and 2: Minimal Residual Disease (MRD) negative Complete Response (CR) rate at 12 months(12 months)
- Phase 1b and 2: Time to response (TTR)(Through study completion, a minimum of 2 years.)
- Phase 1b and 2: Progression-free survival (PFS)(Through study completion, a minimum of 2 years.)
- Phase 1b and 2: Overall survival (OS)(Through study completion, a minimum of 2 years.)
- Ph1b and 2: Humoral Immunogenicity(Through study completion, a minimum of 2 years.)
- Phase 2: Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) IL355 Bone Pain and Health-Related Quality of Life Scale Scores(Through study completion, a minimum of 2 years.)
- Phase 2: Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) IL356 Physical Function and Fatigue Subscale Scores(Through study completion, a minimum of 2 years.)