A First-in-human, Phase I/II, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of EMB-06 in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 10
- 主要终点
- Incidence and severity of adverse events
研究概览
简要总结
The primary purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for EMB-06 and to characterize the safety and tolerability of EMB-06 at the RP2Ds. Pharmacokinetics (PK), immunogenicity, and the anti-multiple myeloma activity of EMB-06 will also be assessed.
详细描述
This is a Phase I/II, multi-center, open label, multiple-dose, first in human study, designed to assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for EMB-06 in patients with relapsed or refractory multiple myeloma. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.
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
- •Able to understand and willing to sign the informed consent form (ICF)
- •Patients who have been diagnosed with multiple myeloma according to IMWG diagnostic criteria 2014 and have relapsed or refractory multiple myeloma with at least one measurable lesion.
- •The patient must have received at least two lines (for patients in the US, at least three lines which should include anti-CD38 antibody) of prior antimyeloma therapies, and must have received treatment with proteasome inhibitors, immunomodulatory agents, and if accessible, an anti-CD38 targeting monoclonal antibody.
- •ECOG performance status 0 or 1 for phase I, and ≤2 for phase II.
- •Adequate organ function and reasonable laboratory test results to participate in the trial.
- •Highly effective contraception
排除标准
- •Life expectancy is less than 3 months.
- •Patient participated in any other clinical study within 1 month prior to enrollment in this clinical study.
- •Patients with ongoing AE.
- •Previously treated with any BCMA-targeted therapy.(Exception: in Phase 2 portion, up to 10 patients who have received prior anti-BCMA ADC or BCMA targeted CAR-T can be enrolled)
- •History of allogeneic stem cell transplantation.
- •Previously treated with the following anti-tumor therapy (prior to first dosing of EMB-06)
- •Treated with monoclonal antibody for multiple myeloma within 28 days
- •Treated with proteasome inhibitors within 14 days
- •Treated with immunomodulatory agents within 14 days
- •Treated with cytotoxic therapy within 14 days
- •Received investigational drug within 28 days or at least 5 half-lives, whichever is shorter (if a, b, c, d not applicable)
- •Received radiotherapy within 21 days. Except that the radiation portal covered ≤ 5% of the bone marrow reserve, the patient will be eligible to participate in the study regardless of the end date of radiation therapy
- •Plasmapheresis within 7 days
- •Patient received autologous stem cell transplantation within 12 weeks prior to the start of study treatment.
- •Active or historically multiple myeloma related central nervous system involvement.
- •Patients requiring high dose of systemic treatment with corticosteroids.
- •Patients with active infections, including COVID-19, hepatitis, etc..
- •History of severe allergic reactions
- •Patients with severe or uncontrolled cardiovascular disorder requiring treatment
- •Pre-existing other serious medical conditions
研究组 & 干预措施
EMB-06
In Phase I part: participants enrolled at different time will receive EMB-06 by IV infusion at different ascending dose levels.
In Phase II part: participants will receive EMB-06 by IV infusion at previously defined RP2D.
干预措施: EMB-06 (Biological)
结局指标
主要结局
Incidence and severity of adverse events
时间窗: Screening up to follow-up (30 days after the last dose)
Incidence and severity of AE.
Incidence of dose interruptions.
时间窗: Screening up to follow-up (30 days after the last dose)
Incidence of dose interruptions of EMB-06 during treatment as a measure of tolerability.
The incidence of DLTs during treatment.
时间窗: First infusion to the end of Cycle 1 (each cycle is 28 days)
The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and are specifically defined in study protocol.
Incidence of serious adverse events (SAE)
时间窗: Screening up to follow-up (30 days after the last dose)
Incidence of SAE
Dose intensity
时间窗: Screening up to follow-up (30 days after the last dose)
Actual amount of drug taken by patients divided by the planned amount.
Overall Response Rate (ORR)
时间窗: From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months
Measured by IMWG criteria, only applicable in Phase II part
次要结局
- Terminal half-life (T1/2) of EMB-06.(Through treatment until EOT visit, expected average 6 months)
- Maximum serum concentration (Cmax) of EMB-06.(Through treatment until EOT visit, expected average 6 months)
- Area under the serum concentration-time curve (AUC) of EMB-06.(Through treatment until EOT visit, expected average 6 months)
- Steady state volume of distribution (Vss) of EMB-06.(Through treatment until EOT visit, expected average 6 months)
- Average concentration over a dosing interval (Css, avg) of EMB-06.(Through treatment until EOT visit, expected average 6 months)
- Progression free survival (PFS) of EMB-06 as assessed by IMWG criteria.(From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months)
- Trough concentration (Ctrough) of EMB-06.(Through treatment until EOT visit, expected average 6 months)
- Systemic clearance (CL) of EMB-06.(Through treatment until EOT visit, expected average 6 months)
- Incidence and titer of anti-drug antibodies stimulated by EMB-06.(Up to End of Treatment Follow Up Period (30 days after the last dose))
- Duration of response of EMB-06 as assessed by IMWG criteria(From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months)