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CompletedNCT05673057Updated Sep 25, 2026

Study of MP0533 in Patients Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Phase 1 interventional study of MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 1 and MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 2-Arm A in Leukemia, Myeloid and Acute, sponsored by Molecular Partners AG. Completed at 9 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-25.

Sponsored by Molecular Partners AG · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
80
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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)

02

Conditions studied

  • Leukemia
  • Myeloid
  • Acute
  • Newly Diagnosed

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Keywords

  • DARPin
  • CD33
  • CD123
  • CD70
  • T-cell/CD3 engager
  • multispecific
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
80 participants (actual)

Study arms

  • 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

  • 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

  • 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

  • Experimental
    Dose expansion (Arm A)

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

    Drug: MP0533 with Obinutuzumab pretreatment

  • 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

  • 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

Interventions

  • DrugMP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 1

    MP0533 is administered by intravenous infusion

    Also known as: Part 1

  • DrugMP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 2-Arm A

    * MP0533 is administered by intravenous infusion * Obinutuzumab pretreatment administered

    Also known as: Part 2 - Arm A

  • DrugMP0533 (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

    Also known as: Part 2 - Arm B

  • DrugMP0533 with Obinutuzumab pretreatment

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

    Also known as: Arm A

  • DrugMP0533 + 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

    Also known as: Arm B relapsed/refractory AML

  • DrugMP0533 + 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

    Also known as: Arm B in treatment naïve patients

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: from start of treatment to end of first cycle (day 1 - 28)

  2. 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

    Time frame: throughout the study (on average 3 months)

Secondary outcomes

  1. Serum Concentration-time profiles (max. serum)

    Determination of PK parameters including (but not limited to) maximum serum concentration (Cmax)

    Time frame: throughout the study (on average 1 year)

  2. Serum Concentration-time profiles (at Cmax (Tmax))

    Determination of PK parameters including (but not limited to) time at Cmax (Tmax)

    Time frame: throughout the study (on average 1 year)

  3. Serum Concentration-time profiles (min. serum concentration)

    Determination of PK parameters including (but not limited to) minimal serum concentration (Cmin)

    Time frame: throughout the study (on average 1 year)

  4. Area under the concentration-time curve (AUC)

    Pharmacokinetic (PK) analysis of MP0533

    Time frame: throughout the study (on average 1 year)

  5. Total Clearance (CL)

    PK analysis of MP0533

    Time frame: throughout the study (on average 1 year)

  6. Volume of distribution (Vd)

    PK analysis of MP0533

    Time frame: throughout the study (on average 1 year)

  7. Half-life (t1/2)

    PK analysis of MP0533

    Time frame: throughout the study (on average 1 year)

  8. 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

    Time frame: throughout the study (on average 1 year)

  9. 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

    Time frame: throughout the study (on average 1 year)

  10. Duration of response (DoR)

    time from the start date of CR, CRh, CRi, MLFS or PR to relapse or death

    Time frame: throughout the study (on average 1 year)

  11. Overall survival (OS)

    time from the date of first study treatment administration to the date of death

    Time frame: throughout the study (up to 3 years)

  12. Transfusion-Independence (TI)

    portion of subjects who achieved RBC/platelet transfusion independence post baseline

    Time frame: throughout the study (on average 1 year)

  13. Number of patients proceeding to a stem cell transplantation

    Number of patients proceeding to a stem cell transplantation

    Time frame: throughout the study (on average 1 year)

06

Study locations

9 sites
  • CHU Bordeaux
    Bordeaux, France
  • AP-HP Hôpital Saint-Louis
    Paris, 75010, France
  • IUCT Oncopole
    Toulouse, France
  • Vilnius University Hospital Santaros Klinikos
    Vilnius, Lithuania
  • Groningen UMC
    Groningen, Provincie Groningen, Netherlands
  • Amsterdam UMC - Locatie VUmc
    Amsterdam, Netherlands
  • Erasmus MC
    Rotterdam, Netherlands
  • Inselspital, Universitaetsspital Bern
    Bern, Canton of Bern 3010, Switzerland
  • Universitaetsspital Zuerich
    Zurich, Canton of Zurich 8006, Switzerland
07

References and documents

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. PubMed 38683145 ↗
08

Registry details

Key details

Study ID
NCT05673057
Lead sponsor
Molecular Partners AG
Responsible party
Sponsor
First posted
Jan 6, 2023
Start date
Dec 29, 2022
Primary completion
May 29, 2026
Completion
Sep 14, 2026
Last update
Sep 25, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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