A Phase 1, First-in-Human, Dose Escalation Study of MGD024, a CD123 x CD3 Bispecific DART Molecule, in Patients With Select Relapsed or Refractory Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- MacroGenics
- 入组人数
- 130
- 试验地点
- 15
- 主要终点
- Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation.
研究概览
简要总结
CP-MGD024-01 is a Phase 1, open-label, multi-center study of MGD024 as a single agent in participants with select blood cancers that have not responded to treatment with standard therapies or who have relapsed after treatment. The study is designed to determine the safety, tolerability, pharmacokinetics (affect of the body on the drug), pharmacodynamic (affect of the drug on the body), immunogenicity (development of antibodies against the drug), and preliminary anti-cancer effect of MGD024.
Participants will receive treatment with MGD024 in consecutive 28-day cycles for a study treatment period of up to 12 cycles (approximately 1 year) or until treatment or study discontinuation criteria are met. Response assessments will be performed after Cycle 1 and then after every even numbered cycle starting with Cycle 2 until progression or study treatment discontinuation. Participants will be checked for side effects throughout the study.
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
- •Adult patients at least 18 years of age, able to provide informed consent and willing to comply with all study procedures.
- •Participants with
- •primary or secondary acute myeloid leukemia (AML) except acute promyelocytic leukemia,
- •primary or secondary myelodysplastic syndrome (MDS) with prognostic score of >3 and <20% bone marrow blasts,
- •classical Hodgkin lymphoma (cHL),
- •chronic myelogenous leukemia (CML),
- •b-cell acute lymphocytic leukemia (B-ALL),
- •hariy cell leukemia (HCL),
- •advanced systemic mastocytosis (ASM), or
- •blastic plasmacytoid dendritic cell neoplasm (BPDCM)
- •Relapsed after or refractory to at least one prior line of therapy and with no available potentially curative treatment option.
- •Evidence of at least 20% of malignant cells with CD123 expression.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Life expectancy of at least 12 weeks.
- •Acceptable laboratory values, and heart function.
- •Continuing side effects of prior treatment are mild
- •Women and men of childbearing potential must agree to use highly effective forms of contraception throughout the study through 4 months after the last dose of MGD024.
排除标准
- •Prior treatment with an anti-CD123-directed agent (except patients with BPDCN, who are allowed to have received prior tagraxofusp).
- •Known involvement of central nervous system (CNS) by the disease under investigation.
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient.
- •Systemic anti-cancer therapy, investigational therapy, corticosteroids or other immune suppressive drugs within 14 days of first dose
- •Vaccination with any live virus vaccine within 4 weeks prior to first dose. Inactivated annual influenza and SARS-CoV-2 vaccination are allowed.
研究组 & 干预措施
Dose Escalation
Escalating doses of MGD024 will be assigned based on safety and tolerability of the previous dose level.
干预措施: MGD024 (Drug)
结局指标
主要结局
Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation.
时间窗: Throughout study participation, up to 12 months.
Observation of side effects determines the highest safe dose for further study
Number of severe side effects in patients receiving MGD024
时间窗: First 28 days of the study
Observation of side effects determines the highest safe dose for further study
次要结局
- Mean maximum concentration(Throughout study participation, up to 12 months.)
- Mean area under the concentration-time curve (AUC)(Throughout study participation, up to 12 months.)
- Number of participants with anti-drug antibody formation(Throughout study participation, up to 12 months.)
- Outcome of CRS event in participants treated with tocilizumab or etanercept(Throughout study participation, up to 12 months.)
- Overall response rate(Disease response assessment on Day 28, Day 56, then every 56 days throughout the study, up to 12 months.)
- Complete response rate(Disease response assessment on Day 28, Day 56, then every 56 days throughout the study, up to 12 months.)
- Number of participants with AEs and SAEs occurring after administration of tocilizumab or etanercept for cytokine release syndrome (CRS)(Throughout study participation, up to 12 months.)
- Median progression free survival(Disease response is assessed approximately every 56 days throughout the study, up to 12 months.Assessed from Day 1 throughout the study until individual participant discontinuation, up to 12 months. Survival from Day 1 throughout the study.)
- Median time to response(Disease response is assessed approximately every 56 days throughout the study, up to 12 months.)
- Median duration of response(Disease response is assessed approximately every 56 days throughout the study, up to 12 months.)
- Overall survival(Assessed from Day 1 throughout the study until individual participant study discontinuation, up to 12 months.)
- Number of participants with changes in cytokines or C-reactive protein after administration of tocilizumab or etanercept(Throughout study participation, up to 12 months.)