临床试验/NCT05673057

NCT05673057进行中（未招募）1 期

A Phase 1/2a, First-in-human, Open-label, Multicenter, Dose Escalation Study of MP0533 in Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Molecular Partners AG18 个研究点分布在 4 个国家目标入组 249 人开始时间: 2022年12月29日最近更新: 2026年6月9日

适应症

干预措施

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Molecular Partners AG
入组人数: 249
试验地点: 18
主要终点: Phase 1 dose escalation: Recommended Phase 2 Dose Regimen and/or Maximum Tolerated Dose Regimen

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相关资讯

研究概览

简要总结

The purpose of this study is to evaluate the safety, tolerability, and preliminary activity of MP0533 in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

研究设计

研究类型: Interventional
分配方式: Non Randomized
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

•Has signed and dated written informed consent prior to performing any study procedure, including screening
•Diagnosis of relapsed/refractory AML or relapsed/refractory MDS/AML according to the ELN recommendation
•Age ≥18 years old on the day of signing informed consent
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
•Anticipated life expectancy ≥ 12 weeks by investigator judgement
•White blood count (WBC) ≤ 15G/L at day of trial drug infusion
•Adequate renal and hepatic function
•Is using highly effective contraception, for females of childbearing potential and for men

排除标准

•Mixed phenotype acute leukemia
•Patients with favorable AML mutations according to ELN recommendation 2022 and 2024
•Allogeneic HCT within the last 3 months and/or eligibility for standard 2nd line of targeted therapy, like gilteritinib for FLT3 mutated AML, unless this therapeutic option has already been given and proven ineffective (patient relapsed or resistant to), or contraindicated, or confounding mutations exist, or there is a lack of access to this recommended therapy.
•More than 2 prior lines of anti-leukemic therapy
•Active GvHD requiring immune-suppressive therapy
•Use of immunosuppressive drugs
•Clinical signs of AML in the central nervous system
•Major surgery within 28 days prior to start of study medication
•Other malignancy requiring active therapy, but adjuvant endocrine therapy is allowed
•Any uncontrolled active infection
•Treatment with investigational agents or agents targeting CD33, CD123 or CD70 within 4 weeks or five times the half-life of the agent, whichever is longer, prior to start of trial medication
•Left ventricular ejection fraction of < 50% on echocardiographic exam at screening
•History or evidence of clinically significant cardiovascular disease
•Pulmonary disease with clinically relevant hypoxia
•Active hepatitis
•Concurrent enrolment in another clinical trial, unless it is an observational (non-interventional) study or it is the follow-up period of an interventional study
•Known hypersensitivity to any of the excipients of the investigational medicinal product (IMP), i.e. finished MP0533 drug
•Dose Expansion Group (Arm B in treatment-naïve patients only):
•Treatment-naïve patients who are eligible to AZA+VEN as standard of care
•Dose Escalation and Expansion Groups (Arm B only):
•received VEN in prior treatment lines
•received strong and/or moderate CYP3A inducers within 7 days before the initiation of AZA/VEN regimen;
•Has consumed grapefruit, grapefruit products, Seville oranges or Starfruit within 3 days before the initiation of AZA/VEN regimen;
•Has a malabsorption syndrome or other condition that precludes the enteral route of administration of VEN.

研究组 & 干预措施

Dose escalation (Part 1)

Experimental

• MP0533 is administered by intravenous infusion

干预措施: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 1 (Drug)

Dose escalation (Part 2 - Arm A)

Experimental

MP0533 is administered by intravenous infusion
Obinutuzumab pretreatment administered

干预措施: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 2-Arm A (Drug)

Dose escalation (Part 2 - Arm B)

Experimental

MP0533 is administered by intravenous infusion
Azacitidine is administered by subcutaneous injection for 7 days per cycle
Venetoclax is administered orally for 14 days per cycle
Optional Obinutuzumab pretreatment administered

干预措施: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) + azacitidine + venetoclax (Drug)

Dose expansion (Arm A)

Experimental

MP0533 is administered by intravenous infusion at densified dosing schedule
Obinutuzumab pretreatment administered

干预措施: MP0533 with Obinutuzumab pretreatment (Drug)

Dose expansion (Arm B relapsed/refractory AML)

Experimental

MP0533 is administered by intravenous infusion
Azacitidine is administered by subcutaneous injection for 7 days per cycle
Venetoclax is administered orally for 14 days per cycle
Optional Obinutuzumab pretreatment administered

干预措施: MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B in treatment naïve patients (Drug)

Dose expansion (Arm B in treatment naïve patients)

Experimental

MP0533 is administered by intravenous infusion
Azacitidine is administered by subcutaneous injection for 7 days per cycle
Venetoclax is administered orally for 14 days per cycle
Optional obinutuzumab pretreatment administered

干预措施: MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B relapsed/refractory AML (Drug)

结局指标

主要结局

Phase 1 dose escalation: Recommended Phase 2 Dose Regimen and/or Maximum Tolerated Dose Regimen

时间窗: from start of treatment to end of first cycle (day 1 - 28)

Incidence of dose limiting toxicities, assessment of toxicity/safety, pharmacokinetic and efficacy parameters

Phase 2 dose extension: Overall Response Rate

时间窗: throughout the study (on average 3 months)

Best overall response of complete remission (CR), complete remission with partial hematological recovery (CRh), complete remission with incomplete hematological recovery (CRi), morphologic leukemia-free state (MLFS) and partial remission (PR) according to the European LeukemiaNet (ELN) response criteria 2022

次要结局

Serum Concentration-time profiles (max. serum)(throughout the study (on average 1 year))
Serum Concentration-time profiles (at Cmax (Tmax))(throughout the study (on average 1 year))
Serum Concentration-time profiles (min. serum concentration)(throughout the study (on average 1 year))
Area under the concentration-time curve (AUC)(throughout the study (on average 1 year))
Total Clearance (CL)(throughout the study (on average 1 year))
Volume of distribution (Vd)(throughout the study (on average 1 year))
Half-life (t1/2)(throughout the study (on average 1 year))
Incidence of adverse events (AEs) as a measure of safety(throughout the study (on average 1 year))
Event free survival (EFS)(throughout the study (on average 1 year))
Duration of response (DoR)(throughout the study (on average 1 year))
Overall survival (OS)(throughout the study (up to 3 years))
Transfusion-Independence (TI)(throughout the study (on average 1 year))
Number of patients proceeding to a stem cell transplantation(throughout the study (on average 1 year))

研究者

发起方

Molecular Partners AG

申办方类型

Industry

责任方

Sponsor

研究点 (18)

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