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

Phase 1

Recruiting

Interventions: Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70)

Brief Summary: 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)

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Dose escalation	MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70)	-
Dose expansion	MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70)	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Locations (9): IUCT Oncopole
🇫🇷
Toulouse, France
AP-HP Hôpital Saint-Louis
🇫🇷
Paris, France
CHU Bordeaux
🇫🇷
Bordeaux, France
Amsterdam UMC - Locatie VUmc
🇳🇱
Amsterdam, Netherlands
Groningen UMC
🇳🇱
Groningen, Netherlands
Erasmus MC
🇳🇱
Rotterdam, Netherlands
Inselspital, Universitaetsspital Bern
🇨🇭
Bern, Switzerland
Vilnius University Hospital Santaros Klinikos
🇱🇹
Vilnius, Lithuania
Universitaetsspital Zuerich
🇨🇭
Zuerich, Switzerland