Study of MP0533 in Patients Acute Myeloid Leukemia or Myelodysplastic Syndrome

Molecular Partners

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Newly Diagnosed

Acute

Myeloid

Leukemia

Treatments

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

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

Drug: MP0533 with Obinutuzumab pretreatment

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

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

Funder types

Industry

Identifiers

NCT05673057

MP0533-CP101

2022-002432-31 (EudraCT Number)

2023-505259-39-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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)

Enrollment

249 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

249 participants in 6 patient groups

Dose escalation (Part 1)

Experimental group

Description:

• MP0533 is administered by intravenous infusion

Treatment:

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

Dose escalation (Part 2 - Arm A)

Experimental group

Description:

* MP0533 is administered by intravenous infusion * Obinutuzumab pretreatment administered

Treatment:

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

Dose escalation (Part 2 - Arm B)

Experimental group

Description:

* 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

Treatment:

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

Dose expansion (Arm A)

Experimental group

Description:

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

Treatment:

Drug: MP0533 with Obinutuzumab pretreatment

Dose expansion (Arm B relapsed/refractory AML)

Experimental group

Description:

Treatment: