Study of MP0533 in Patients Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT ID: NCT05673057

Last Updated: 2025-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

249 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-29

Study Completion Date

2029-12-31

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 acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Detailed Description

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Conditions

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Leukemia Myeloid Acute Newly Diagnosed

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose escalation (Part 1)

• MP0533 is administered by intravenous infusion

Group Type EXPERIMENTAL

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

Intervention Type DRUG

MP0533 is administered by intravenous infusion

Dose escalation (Part 2 - Arm A)

* MP0533 is administered by intravenous infusion
* Obinutuzumab pretreatment administered

Group Type EXPERIMENTAL

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

Intervention Type DRUG

* MP0533 is administered by intravenous infusion
* Obinutuzumab pretreatment administered

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

Group Type EXPERIMENTAL

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

Intervention Type 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

Dose expansion (Arm A)

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

Group Type EXPERIMENTAL

MP0533 with Obinutuzumab pretreatment

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

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

Intervention Type 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

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

Group Type EXPERIMENTAL

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

Intervention Type 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

Interventions

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

MP0533 is administered by intravenous infusion

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

MP0533 with Obinutuzumab pretreatment

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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Part 1 Part 2 - Arm A Part 2 - Arm B Arm A Arm B relapsed/refractory AML Arm B in treatment naïve patients

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 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Molecular Partners AG

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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CHU Bordeaux

Bordeaux, , France

Site Status RECRUITING

AP-HP Hôpital Saint-Louis

Paris, , France

Site Status RECRUITING

IUCT Oncopole

Toulouse, , France

Site Status RECRUITING

Vilnius University Hospital Santaros Klinikos

Vilnius, , Lithuania

Site Status RECRUITING

Groningen UMC

Groningen, Provincie Groningen, Netherlands

Site Status RECRUITING

Amsterdam UMC - Locatie VUmc

Amsterdam, , Netherlands

Site Status RECRUITING

Erasmus MC

Rotterdam, , Netherlands

Site Status RECRUITING

Inselspital, Universitaetsspital Bern

Bern, Canton of Bern, Switzerland

Site Status RECRUITING

Universitaetsspital Zuerich

Zurich, Canton of Zurich, Switzerland

Site Status RECRUITING

Countries

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France Lithuania Netherlands Switzerland

Central Contacts

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Medical Director MPAG

Role: CONTACT

+41 44 755 77 00

References

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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.

Reference Type DERIVED
PMID: 38683145 (View on PubMed)

Other Identifiers

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2023-505259-39-00

Identifier Type: CTIS

Identifier Source: secondary_id

2022-002432-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MP0533-CP101

Identifier Type: -

Identifier Source: org_study_id

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