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

Sponsor

Molecular Partners AG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05673057

Collaborator

(none)

Enrollment

Locations

Arms

59.1

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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)

Condition or Disease	Intervention/Treatment	Phase
Leukemia Relapsed Myeloid Acute	Drug: MP0533 (multispecific DARPin CD3 Engager Targeting CD33, CD123 and CD70)	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Dec 29, 2022

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose escalation	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. Other Names: DARPin
Experimental: Dose expansion	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. Other Names: DARPin

Arm

Intervention/Treatment

Experimental: Dose escalation

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.

Other Names:

DARPin

Experimental: Dose expansion

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

Other Names:

DARPin

Outcome Measures

Primary Outcome Measures

Phase 1 dose escalation: Recommended Phase 2 Dose Regimen and/or Maximum Tolerated Dose Regimen [from start of treatment to end of first cycle (day 1 - 28)]
Incidence of dose limiting toxicities, assessment of toxicity/safety, pharmacokinetic and efficacy parameters
Phase 2 dose extension: Overall Response Rate [throughout the study (on average 3 months)]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Amsterdam UMC - Locatie VUmc	Amsterdam	Netherlands
2	Groningen UMC	Groningen	Netherlands
3	Erasmus MC	Rotterdam	Netherlands
4	Inselspital, Universitaetsspital Bern	Bern	Switzerland	3010
5	Universitaetsspital Zuerich	Zuerich	Switzerland	8006