Study of MP0533 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

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

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

Conditions
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Leukemia, Relapsed, Myeloid, Acute

Intervention / Treatment
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* Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed and dated written informed consent prior to performing any study procedure, including screening Diagnosis of AML or MDS/AML according to the ELN, refractory or relapsed to pretreatment with hypomethylating agents (HMA) (with or without venetoclax), induction chemotherapy or allogeneic hematopoietic cell transplantation (HCT) 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 Adequate renal and hepatic function: Is using highly effective contraception, for females of childbearing potential and for men Exclusion Criteria: Allogeneic HCT within the last 3 months Active GvHD requiring immune-suppressive therapy Use of immunosuppressive drugs Symptoms of leukostasis (prior hydroxyurea allowed) 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 active infection requiring the use of parenteral antimicrobial agents or that is grade >2 Treatment with investigational agents and/or agents targeting CD33, CD123 or CD70 within 4 weeks 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br> | Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70)<br>* Phase 1 comprises the dose-escalation part of the study and is designed to determine the recommended phase 2a dose regimen (RP2D-R) and/or the maximum tolerated dose-regimen (MTD-R) for MP0533 monotherapy. Once the RP2D-R or MTD-R has been selected based on the dose escalation part, the study will proceed into the phase 2 expansion part and up to 30 additional patients will be treated.<br>* Other names: DARPin;|
| Experimental: Dose expansion<br> | Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70)<br>* Phase 1 comprises the dose-escalation part of the study and is designed to determine the recommended phase 2a dose regimen (RP2D-R) and/or the maximum tolerated dose-regimen (MTD-R) for MP0533 monotherapy. Once the RP2D-R or MTD-R has been selected based on the dose escalation part, the study will proceed into the phase 2 expansion part and up to 30 additional patients will be treated.<br>* Other names: DARPin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 dose escalation: Recommended Phase 2 Dose Regimen and/or Maximum Tolerated Dose Regimen | Incidence of dose limiting toxicities, assessment of toxicity/safety, pharmacokinetic and efficacy parameters | from start of treatment to end of first cycle (day 1 - 28) | 
| Phase 2 dose extension: Overall Response Rate | 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 | throughout the study (on average 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration-time profiles | Determination of PK parameters including (but not limited to) maximum serum concentration (Cmax) | throughout the study (on average 1 year) | 
| Serum Concentration-time profiles | Determination of PK parameters including (but not limited to) time at Cmax (Tmax) | throughout the study (on average 1 year) | 
| Serum Concentration-time profiles | Determination of PK parameters including (but not limited to) minimal serum concentration (Cmin) | throughout the study (on average 1 year) | 
| Area under the concentration-time curve (AUC) | Pharmacokinetic (PK) analysis of MP0533 | throughout the study (on average 1 year) | 
| Total Clearance (CL) | PK analysis of MP0533 | throughout the study (on average 1 year) | 
| Volume of distribution (Vd) | PK analysis of MP0533 | throughout the study (on average 1 year) | 
| Half-life (t1/2) | PK analysis of MP0533 | throughout the study (on average 1 year) | 
| Incidence of adverse events (AEs) as a measure of safety | Type, incidence and severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | throughout the study (on average 1 year) | 
| Event free survival (EFS) | time from the date of first study treatment administration to the date of treatment failure, hematologic relapse from CR/CRh/CRi or death from any cause | throughout the study (on average 1 year) | 
| Duration of response (DoR) | time from the start date of CR, CRh, CRi, MLFS or PR to relapse or death | throughout the study (on average 1 year) | 
| Overall survival (OS) | time from the date of first study treatment administration to the date of death | throughout the study (up to 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DARPin, CD33, CD123, CD70, T-cell/CD3 engager, multispecific