Study of MP0533 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Leukemia Clinical Trial

Official title:

A Phase 1/2a, First-in-human, Open-label, Multicenter, Dose Escalation Study of MP0533 in Patients With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05673057
• Other study ID #: MP0533-CP101
• Secondary ID: 2022-002432-31
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 29, 2022
• Est. completion date: December 2027

Study information

• Verified date: January 2024
• Source: Molecular Partners AG
• Contact: Medical DirectorG MPAG
• Phone: +41 44 755 77 00
• Email: info[@]molecularpartners.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, and preliminary activity of MP0533 in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has signed and dated written informed consent prior to performing any study procedure, including screening
• Diagnosis of AML or MDS/AML according to the ELN, refractory or relapsed to pretreatment with hypomethylating agents (HMA) (with or without venetoclax), induction chemotherapy or allogeneic hematopoietic cell transplantation (HCT)
• 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
• Adequate renal and hepatic function:
• Is using highly effective contraception, for females of childbearing potential and for men

Exclusion Criteria:

• Allogeneic HCT within the last 3 months
• Active GvHD requiring immune-suppressive therapy
• Use of immunosuppressive drugs
• Symptoms of leukostasis (prior hydroxyurea allowed)
• 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 active infection requiring the use of parenteral antimicrobial agents or that is grade >2
• Treatment with investigational agents and/or agents targeting CD33, CD123 or CD70 within 4 weeks 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
• 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

Related Conditions & MeSH terms

• Acute
• Leukemia
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myeloid
• Preleukemia
• Relapsed

Intervention

Drug:
• MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70)
Phase 1 comprises the dose-escalation part of the study and is designed to determine the recommended phase 2a dose regimen (RP2D-R) and/or the maximum tolerated dose-regimen (MTD-R) for MP0533 monotherapy. Once the RP2D-R or MTD-R has been selected based on the dose escalation part, the study will proceed into the phase 2 expansion part and up to 30 additional patients will be treated.

Locations

Country	Name	City	State
France	CHU Bordeaux	Bordeaux
France	AP-HP Hôpital Saint-Louis	Paris
France	IUCT Oncopole	Toulouse
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Netherlands	Amsterdam UMC - Locatie VUmc	Amsterdam
Netherlands	Groningen UMC	Groningen
Netherlands	Erasmus MC	Rotterdam
Switzerland	Inselspital, Universitaetsspital Bern	Bern
Switzerland	Universitaetsspital Zuerich	Zuerich

Sponsors (1)

Lead Sponsor	Collaborator
Molecular Partners AG

Countries where clinical trial is conducted

France,  Lithuania,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Serum Concentration-time profiles	Determination of PK parameters including (but not limited to) maximum serum concentration (Cmax)	throughout the study (on average 1 year)
Secondary	Serum Concentration-time profiles	Determination of PK parameters including (but not limited to) time at Cmax (Tmax)	throughout the study (on average 1 year)
Secondary	Serum Concentration-time profiles	Determination of PK parameters including (but not limited to) minimal serum concentration (Cmin)	throughout the study (on average 1 year)
Secondary	Area under the concentration-time curve (AUC)	Pharmacokinetic (PK) analysis of MP0533	throughout the study (on average 1 year)
Secondary	Total Clearance (CL)	PK analysis of MP0533	throughout the study (on average 1 year)
Secondary	Volume of distribution (Vd)	PK analysis of MP0533	throughout the study (on average 1 year)
Secondary	Half-life (t1/2)	PK analysis of MP0533	throughout the study (on average 1 year)
Secondary	Incidence of adverse events (AEs) as a measure of safety	Type, incidence and severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	throughout the study (on average 1 year)
Secondary	Event free survival (EFS)	time from the date of first study treatment administration to the date of treatment failure, hematologic relapse from CR/CRh/CRi or death from any cause	throughout the study (on average 1 year)
Secondary	Duration of response (DoR)	time from the start date of CR, CRh, CRi, MLFS or PR to relapse or death	throughout the study (on average 1 year)
Secondary	Overall survival (OS)	time from the date of first study treatment administration to the date of death	throughout the study (up to 3 years)