Study of MP0533 in Patients Acute Myeloid Leukemia or Myelodysplastic Syndrome

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)

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)

Study Overview

• Status: Recruiting
• Conditions: Leukemia; Newly Diagnosed; Acute; Myeloid
• Intervention / Treatment: Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 1; Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 2-Arm A; Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) + azacitidine + venetoclax; Drug: MP0533 with Obinutuzumab pretreatment; Drug: MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B in treatment naïve patients; Drug: MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B relapsed/refractory AML

• Study Type: Interventional
• Enrollment (Estimated): 249
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director MPAG; Phone Number: +41 44 755 77 00; Email: info@molecularpartners.com

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CHU Bordeaux
  • Paris, France, 75010
    • Recruiting
    • AP-HP Hôpital Saint-Louis
  • Toulouse, France
    • Recruiting
    • Iuct Oncopole
• Lithuania
  • Vilnius, Lithuania
    • Recruiting
    • Vilnius University Hospital Santaros Klinikos
• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC - Locatie VUmc
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus MC
  • Provincie Groningen
    • Groningen, Provincie Groningen, Netherlands
      • Recruiting
      • Groningen UMC
• Switzerland
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3010
      • Recruiting
      • Inselspital, Universitaetsspital Bern
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8006
      • Recruiting
      • Universitaetsspital Zuerich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 2022.
• 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

Exclusion Criteria:

• 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):

Inclusion

• Treatment-naïve patients who are eligible to AZA+VEN as standard of care

Dose Escalation and Expansion Groups (Arm B only):

Exclusion

1. received VEN in prior treatment lines
2. received strong and/or moderate CYP3A inducers within 7 days before the initiation of AZA/VEN regimen;
3. Has consumed grapefruit, grapefruit products, Seville oranges or Starfruit within 3 days before the initiation of AZA/VEN regimen;
4. Has a malabsorption syndrome or other condition that precludes the enteral route of administration of VEN.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation (Part 1); • MP0533 is administered by intravenous infusion	Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 1; MP0533 is administered by intravenous infusion; Other Names: Part 1
Experimental: Dose escalation (Part 2 - Arm A); MP0533 is administered by intravenous infusion; Obinutuzumab pretreatment administered	Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 2-Arm A; MP0533 is administered by intravenous infusion; Obinutuzumab pretreatment administered; Other Names: Part 2 - Arm A
Experimental: Dose escalation (Part 2 - Arm B); 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	Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) + azacitidine + venetoclax; 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; Other Names: Part 2 - Arm B
Experimental: Dose expansion (Arm A); MP0533 is administered by intravenous infusion at densified dosing schedule; Obinutuzumab pretreatment administered	Drug: MP0533 with Obinutuzumab pretreatment; MP0533 is administered by intravenous infusion at densified dosing schedule; Obinutuzumab pretreatment administered; Other Names: Arm A
Experimental: Dose expansion (Arm B relapsed/refractory AML); 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	Drug: MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B in treatment naïve patients; 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; Other Names: Arm B in treatment naïve patients
Experimental: Dose expansion (Arm B in treatment naïve patients); 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	Drug: MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B relapsed/refractory AML; 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; Other Names: Arm B relapsed/refractory AML

What is the study measuring?

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
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)
Serum Concentration-time profiles (max. serum)	Determination of PK parameters including (but not limited to) maximum serum concentration (Cmax)	throughout the study (on average 1 year)
Serum Concentration-time profiles (at Cmax (Tmax))	Determination of PK parameters including (but not limited to) time at Cmax (Tmax)	throughout the study (on average 1 year)
Serum Concentration-time profiles (min. serum concentration)	Determination of PK parameters including (but not limited to) minimal serum concentration (Cmin)	throughout the study (on average 1 year)
Transfusion-Independence (TI)	portion of subjects who achieved RBC/platelet transfusion independence post baseline	throughout the study (on average 1 year)
Number of patients proceeding to a stem cell transplantation	Number of patients proceeding to a stem cell transplantation	throughout the study (on average 1 year)

Collaborators and Investigators

• Sponsor: Molecular Partners AG

Publications and helpful links

General Publications

• Bianchi M, Reichen C, Croset A, Fischer S, Eggenschwiler A, Grubler Y, Marpakwar R, Looser T, Spitzli P, Herzog C, Villemagne D, Schiegg D, Abduli L, Iss C, Neculcea A, Franchini M, Lekishvili T, Ragusa S, Zitt C, Kaufmann Y, Auge A, Hanggi M, Ali W, Frasconi TM, Wullschleger S, Schlegel I, Matzner M, Luthi U, Schlereth B, Dawson KM, Kirkin V, Ochsenbein AF, Grimm S, Reschke N, Riether C, Steiner D, Leupin N, Goubier A. The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell-Mediated Killing of AML Leukemic Stem Cells. Cancer Immunol Res. 2024 Jul 2;12(7):921-943. doi: 10.1158/2326-6066.CIR-23-0692.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: December 14, 2022
• First Submitted That Met QC Criteria: January 4, 2023
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: CD33; CD123; CD70; DARPin; T-cell/CD3 engager; multispecific
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax
• Other Study ID Numbers: MP0533-CP101; 2022-002432-31 (EudraCT Number); 2023-505259-39-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No