A study of MP0533 in patients with blood cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Molecular Partners AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Mar 2023 → ongoing

Decision date (initial)

2023-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-505259-39-00

EudraCT number

2022-002432-31

ClinicalTrials.gov

NCT05673057

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Efficacy, Dose response, Pharmacokinetic, Therapy

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 objectives 2

1. Evaluate the preliminary anti-leukemic activity
2. Characterize the pharmacokinetics (PK)

Conditions and MedDRA coding

Acute Myeloid Leukemia (AML)

Regulatory references

Scientific advice from competent authorities

Swissmedic Swiss Agency for Therapeutic Products, Medicines And Healthcare Products Regulatory Agency, Medicines Evaluation Board

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has signed and dated written informed consent prior to performing any study procedure, including screening
2. Diagnosis of relapsed/refractory AML or relapsed/refractory MDS/AML according to the ELN recommendation 2022
3. Age ≥18 years old on the day of signing informed consent
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
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. White blood count (WBC) ≤ 15G/L at day of trial drug infusion (prior hydroxyurea allowed)
8. Is using highly effective contraception, for females of childbearing potential (FCBP) and for men.

Exclusion criteria 23

1. Mixed phenotype acute leukemia
2. Allogeneic HCT within the last 3 months prior to start of trial medication 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.
3. Known hypersensitivity to any of the excipients of the investigational medicinal product (IMP), i.e. finished MP0533 drug
4. Any condition that, in the opinion of the investigator, would interfere with evaluation of the IMP or interpretation of the patient’s data
5. Unable or unwilling to comply with all study requirements for clinical visits, examinations, tests and procedures, and contraception requirements
6. Patient deprived of liberty by a judicial or administrative decision, patient admitted to a social institution or who is under a measure of legal protection, patient hospitalized without consent or who is in an emergency
7. Active GvHD requiring immune-suppressive therapy (other than prednisone (or equivalent) ≤ 10mg/d)
8. Use of immunosuppressive drugs (other than prednisone (or equivalent) ≤10mg/d) in the past 4 weeks
9. Clinical signs of AML in the central nervous system
10. Major surgery within 28 days prior to start of study medication
11. Other malignancy requiring active therapy, but adjuvant endocrine therapy is allowed
12. Left ventricular ejection fraction of < 50% on echocardiographic exam at screening
13. Any uncontrolled active infection
14. 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
15. History or evidence of clinically significant cardiovascular disease defined as at least one of the following criteria: Evidence of poorly controlled arterial hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg); Myocardial infarction or unstable angina pectoris within 6 months before screening; Heart failure (New York Heart Association Class III or IV); Any cardiac arrhythmia that is not well controlled; QT corrected (QTc) prolongation ≥ Grade 2 (> 480 ms) at screening measured on 2 separate electrocardiograms (ECG) at least 10 minutes apart; Clinically significant valvular heart disease
16. Pulmonary disease with clinically relevant hypoxia (need for continuous oxygen inhalation)
17. Known Human Immunodeficiency Virus (HIV)-infected patients who are healthy and have a low risk of Acquired Immunodeficiency Syndrome (AIDS)-related outcomes are eligible, if: No history of AIDS-defining opportunistic infection within past 12 months; Patient agrees to concomitant antiretroviral therapy (ART) if not currently on ART, is on ART for ˃ 4 weeks and has a HIV viral load ˂ 400 copies/mL
18. Active hepatitis.
19. Any vaccines within 28 days before first study drug administration
20. History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥ 2 years before screening and of relatively low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of residual disease; Adequately treated carcinoma in situ without evidence of disease; Cancer patients with incidental histologic findings of prostate cancer that, in the opinion of the investigator, is not deemed to require active therapy may be eligible, pending discussion and approval by the Sponsor
21. Concurrent enrollment in another clinical trial, unless it is an observational (noninterventional) study or it is the follow-up period of an interventional study
22. Patients with favorable AML mutations according to ELN recommendation 2022 and 2024.
23. More than 2 prior lines of anti-leukemic therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Incidence of CRS and non-CRS DLTs during the first cycle of treatment (phase 1 only)
2. Type, incidence and severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
3. Changes in laboratory safety parameters and vital signs
4. 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)

Secondary endpoints 7

1. 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
2. Different levels of CR, CRh, Cri, MLFS and PR according to the ELN response criteria 2022, separately and pooled
3. Event free survival (EFS) based on ELN response criteria 2022
4. Duration of response (DoR) based on ELN response criteria 2022
5. Overall survival (OS) (phase 2a only)
6. Number of patients proceeding to a stem cell transplantation (phase 2a only)
7. Transfusion-Independence (TI)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Molecular Partners AG

Sponsor organisation

Molecular Partners AG

Address

Wagistrasse 14

City

Schlieren

Postcode

8952

Country

Switzerland

Scientific contact point

Organisation

Molecular Partners AG

Contact name

Medical Monitor

Public contact point

Organisation

Molecular Partners AG

Contact name

Medical Monitor

Third parties 4

Locations

3 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications