Study of MP0533 in Patients Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT05673057 | Recruiting Phase 1

• 3 other identifiers: MP0533-CP1012023-505259-39-002022-002432-31
• Study Type: interventional
• Target: 249
• Locations: 4 countries
• Sites: 9

Brief 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)

Conditions

Leukemia; Myeloid; Acute; Newly Diagnosed

Keywords

DARPin; CD33; CD123; CD70; T-cell/CD3 engager; multispecific

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (13)

• 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)

Study Arms (6)

Dose escalation (Part 1)

EXPERIMENTAL

• MP0533 is administered by intravenous infusion

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

Dose escalation (Part 2 - Arm A)

EXPERIMENTAL

* 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

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

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

Dose expansion (Arm A)

EXPERIMENTAL

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

Drug: MP0533 with Obinutuzumab pretreatment

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

Drug: MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B in treatment naïve patients

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

Drug: MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B relapsed/refractory AML

Interventions

MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 1 DRUG

MP0533 is administered by intravenous infusion

Also known as: Part 1

Dose escalation (Part 1)

MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) monotherapy, Part 2-Arm A DRUG

* MP0533 is administered by intravenous infusion * Obinutuzumab pretreatment administered

Also known as: Part 2 - Arm A

Dose escalation (Part 2 - Arm A)

MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70) + azacitidine + venetoclax DRUG

* 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

Dose escalation (Part 2 - Arm B)

MP0533 with Obinutuzumab pretreatment DRUG

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

Also known as: Arm A

Dose expansion (Arm A)

MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B relapsed/refractory AML DRUG

* 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

Dose expansion (Arm B in treatment naïve patients)

MP0533 + azacitidine + venetoclax with optional Obinutuzumab pretreatment, Arm B in treatment naïve patients DRUG

* 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

Dose expansion (Arm B relapsed/refractory AML)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Molecular Partners AG: lead

Study Sites (9)

CHU Bordeaux

Bordeaux, France

RECRUITING

AP-HP Hôpital Saint-Louis

Paris, 75010, France

RECRUITING

IUCT Oncopole

Toulouse, France

RECRUITING

Vilnius University Hospital Santaros Klinikos

Vilnius, Lithuania

RECRUITING

Groningen UMC

Groningen, Provincie Groningen, Netherlands

RECRUITING

Amsterdam UMC - Locatie VUmc

Amsterdam, Netherlands

RECRUITING

Erasmus MC

Rotterdam, Netherlands

RECRUITING

Inselspital, Universitaetsspital Bern

Bern, Canton of Bern, 3010, Switzerland

RECRUITING

Universitaetsspital Zuerich

Zurich, Canton of Zurich, 8006, Switzerland

RECRUITING

Related Publications (1)

• 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.

  PMID: 38683145 DERIVED

MeSH Terms

Conditions

Leukemia

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Medical Director MPAG

CONTACT

+41 44 755 77 00; info@molecularpartners.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2022
• First Posted: January 6, 2023
• Study Start: December 29, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 30, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

LI (1); FR (3); NL (3); CH (2)