A Modular Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With Relapsed or Refractory B-Cell Malignancies (TITANium)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 174
- 试验地点
- 33
- 主要终点
- Frequency of dose limiting toxicities (DLTs).
研究概览
简要总结
This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious in participants with Relapsed or Refractory B-Cell Malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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;
- •Histologically documented CD20+ mature B-cell neoplasm
- •Large B-cell lymphoma
- •Follicular lymphoma
- •Mantle cell lymphoma
- •Chronic lymphocytic leukemia
- •Small lymphocytic lymphoma
- •Relapsed, progressive and/or refractory disease following at least 2 prior lines of therapy;
- •ECOG performance status of ≤ 2 (< 2 in EU countries).
- •The above is a summary, other inclusion criteria details may apply.
排除标准
- •Any neoplasm histology not specified in the IC section;
- •Active CNS involvement in lymphoma;
- •CNS pathology including but not limited to any history of seizure disorder/epilepsy;
- •Prior allogeneic HSCT within 180 days, prior autologous HSCT within 90 days, or cell therapy within 90 days of start of therapy;
- •History of Grade ≥ 3 CRS or Grade ≥ 3 ICANS;
- •Active and uncontrolled infections;
- •Unresolved AEs ≥2 Grade due to prior anticancer therapies, with some exceptions
- •The above is a summary, other exclusion criteria details may apply.
研究组 & 干预措施
Module 1: AZD5492 Monotherapy
AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies.
干预措施: AZD5492 (Drug)
结局指标
主要结局
Frequency of dose limiting toxicities (DLTs).
时间窗: Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).
DLTs are dose-limiting toxicities as defined in the study protocol.
Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events.
时间窗: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
SAEs/AEs leading to discontinuation of AZD5492.
Safety evaluation of AZD5492: Number of participants with treatment-related adverse events.
时间窗: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
Incidence and severity of AEs, AESIs, and SAEs
次要结局
- Overall Response Rate (ORR)(Module 1 - From first dose of AZD5492 up to 2 years after last dose.)
- Complete Response Rate (CR Rate)(Module 1 - From first dose of AZD5492 up to 2 years after last dose.)
- Duration of Response (DoR)(Module 1 - From first dose of AZD5492 up to 2 years after last dose.)
- Progression-free Survival (PFS)(Module 1 - From first dose of AZD5492 up to 2 years after last dose.)
- Overall Survival (OS)(Module 1 - From first dose of AZD5492 up to 2 years after last dose.)
- Pharmacokinetics of AZD5492: serum concentration of study drug(Module 1 - From informed consent until 90 days after last dose of AZD5492.)
- Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax).(Module 1 - From informed consent until 90 days after last dose of AZD5492.)
- Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC).(Module 1 - From informed consent until 90 days after last dose of AZD5492.)
- Pharmacokinetics of AZD5492: apparent clearance(Module 1 - From informed consent until 90 days after last dose of AZD5492.)
- Pharmacokinetics of AZD5492: Half-life (t 1/2)(Module 1 - From informed consent until 90 days after last dose of AZD5492.)
- To determine the immunogenicity of AZD5492(Module 1 - From informed consent until 90 days after last dose of AZD5492.)