relapsed/refractory (R/R) acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MP0533
Product Code: MP0533
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: TBC
Current Sponsor code: MP0533
Other descriptive name: DARP in tar
Sponsors
Molecular Partners AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has signed and dated written informed consent prior to performing any study procedure, including screening 2. Diagnosis of AML or MDS/AML according to the ELN recommendation 2022 (Appendix 12.1 of the protocol), refractory or relapsed to pretreatment with hypomethylating agents (HMA) (with or without venetoclax), induction chemotherapy or allogeneic hematopoietic cell transplantation (HCT) 3. Age =18 years old on the day of signing informed consent 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2 (see Appendix 12.2 of the protocol) 5. Anticipated life expectancy = 12 weeks by investigator judgement 6. Adequate renal and hepatic function: a. Creatinine clearance > 40 mL/min on the basis of Cockcroft-Gault glomerular filtration rate estimation, unless considered AML- or MDS-related b. Serum bilirubin = 2.5 x upper limit of normal (ULN), unless considered AML- or MDS-related or due to Gilbert’s syndrome c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 x ULN, unless considered AML- or MDS-related 7. Is using highly effective contraception, for females of childbearing potential (FCBP) and for men Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Allogeneic HCT within the last 3 months 2. Active GvHD requiring immune-suppressive therapy (other than prednisone (or equivalent) = 10mg/d) 3. Use of immunosuppressive drugs (other than prednisone (or equivalent) =10mg/d) in the past 4 weeks 4. Symptoms of leukostasis (prior hydroxyurea allowed) 5. Clinical signs of AML in the central nervous system 6. Major surgery within 28 days prior to start of study medication 7. Other malignancy requiring active therapy, but adjuvant endocrine therapy is allowed 8. Any active infection requiring the use of parenteral antimicrobial agents or that is grade >2 9. Treatment with agents targeting CD33, CD123 or CD70 within 4 weeks prior to start of trial medication 10. Left ventricular ejection fraction of < 50% on echocardiographic exam at screening 11. History or evidence of clinically significant cardiovascular disease 12. Pulmonary disease with clinically relevant hypoxia 13. Known Human Immunodeficiency Virus (HIV)-infected patients who are healthy and have a low risk of Acquired Immunodeficiency Syndrome (AIDS)-related outcomes may be eligible (see protocol) 14. Active hepatitis B (chronic or acute; HBV) 15. Active hepatitis C (HCV) infection 16. Any vaccines within 28 days before first study drug administration 17. History of another primary malignancy may be excluded (see protocol)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Investigating MP0533 as monotherapy in patients with R/R AML and MDS/AML is to: • Determine the safety and tolerability • Define the recommended phase 2 dose regimen (RP2D-R) and/or the maximum tolerated dose-regimen (MTD-R) (phase 1 only) • Evaluate the preliminary anti-leukemic activity (primary for phase 2a, secondary for phase 1);Secondary Objective: Investigating MP0533 as monotherapy in patients with R/R AML and MDS/AML is to: • Further evaluate the preliminary anti-leukemic activity • Characterize the pharmacokinetics (PK) ;Primary end point(s): - Incidence of CRS and non-CRS DLTs during the first cycle of treatment (phase 1 only) - Type, incidence and severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 - Changes in laboratory safety parameters and vital signs - Overall response rate (ORR) based on best overall response of complete remission, 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 (phase 2a only);Timepoint(s) of evaluation of this end point: Variable. For example, certain assessments will be performed at screening, at week 4, 8 and 12 after the start of study treatment and every 12 weeks (± 1 week) thereafter until PD, withdrawal of consent, death, or study termination, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Determination of PK parameters including (but not limited to) Cmax, time at Cmax (Tmax), minimal serum concentration (Cmin), area under the concentration-time curve (AUC), total CL, volume of distribution (Vd) and t1/2 - Different levels of CR, CRh, CRi, MLFS and PR according to the ELN response criteria 2022, separately and pooled - Event free survival (EFS) based on ELN response criteria 2022 - Duration of response (DoR) based on ELN response criteria 2022 - Overall survival (OS) (phase 2a only) - Reduction of granulocyte-colony stimulating factor (G-CSF) ;Timepoint(s) of evaluation of this end point: Variable | — |
Countries
Lithuania, Netherlands, Switzerland
Contacts
Public ContactChief Medical Officer
Molecular Partners AG
Outcome results
None listed