Clinical trial NCT05673057: Study of MP0533 in Patients Acute Myeloid Leukemia or Myelodysplastic Syndrome
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Leukemia
Myeloid
Acute
Newly Diagnosed
Keywords: DARPin
CD33
CD123
CD70
T-cell/CD3 engager
multispecific
Lead sponsor: Molecular Partners AG
Sponsor class: INDUSTRY
First posted: 2023-01-06
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)


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.

Primary outcomes:
measure: Phase 1 dose escalation: Recommended Phase 2 Dose Regimen and/or Maximum Tolerated Dose Regimen
timeFrame: from start of treatment to end of first cycle (day 1 - 28)
measure: Phase 2 dose extension: Overall Response Rate
timeFrame: throughout the study (on average 3 months)
Secondary outcomes:
measure: Serum Concentration-time profiles (max. serum)
timeFrame: throughout the study (on average 1 year)
measure: Serum Concentration-time profiles (at Cmax (Tmax))
timeFrame: throughout the study (on average 1 year)
measure: Serum Concentration-time profiles (min. serum concentration)
timeFrame: throughout the study (on average 1 year)
measure: Area under the concentration-time curve (AUC)
timeFrame: throughout the study (on average 1 year)
measure: Total Clearance (CL)
timeFrame: throughout the study (on average 1 year)
measure: Volume of distribution (Vd)
timeFrame: throughout the study (on average 1 year)
measure: Half-life (t1/2)
timeFrame: throughout the study (on average 1 year)
measure: Incidence of adverse events (AEs) as a measure of safety
timeFrame: throughout the study (on average 1 year)
measure: Event free survival (EFS)
timeFrame: throughout the study (on average 1 year)
measure: Duration of response (DoR)
timeFrame: throughout the study (on average 1 year)
measure: Overall survival (OS)
timeFrame: throughout the study (up to 3 years)
measure: Transfusion-Independence (TI)
timeFrame: throughout the study (on average 1 year)
measure: Number of patients proceeding to a stem cell transplantation
timeFrame: throughout the study (on average 1 year)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Paris
country: France
facility: AP-HP Hôpital Saint-Louis
city: Toulouse
country: France
facility: IUCT Oncopole
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Locatie VUmc
city: Groningen
country: Netherlands
facility: Groningen UMC
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Bern
country: Switzerland
facility: Inselspital, Universitaetsspital Bern
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich
Study officials:
References: