FLYSYN in MRD Positive AML

This is a first in human, prospective, multicentric, nonrandomized, open-label study to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of the Fc-optimized antibody FLYSYN as monotherapy in adult subjects.

Cohort 1:

Patient 1-3: FLYSYN 0.5 mg/m² body surface area (BSA) day 1

Cohort 2:

Patient 4-6: FLYSYN 0.5 mg/m² body surface area (BSA) day 1 FLYSYN 1.0 mg/m² BSA day 2

Cohort 3:

Patient 7-9: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 4.5 mg/m² BSA day 2

Cohort 4:

Patient 10-12 and 13-18: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 14.5 mg/m² BSA day 2

Cohort 5:

Patient 19-21: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 44.5 mg/m² BSA day 2

Cohort 6:

Patient 22-24 and 25 -31: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 14.5 mg/m² BSA day 2, FLYSYN 15 mg/m² BSA day 15, FLYSYN 15 mg/m² BSA day 29

Eligibility Criteria:
Inclusion Criteria:

* Age ≥18 years at the time of voluntarily signing an IEC-approved informed consent, there is no upper age limit
* Diagnosis of AML according to WHO criteria
* Confirmed FLT3 expression on leukemic cells
* Known mutational status of FLT3 (FLT3-ITD, FLT3-TKD, FLT3 wild type)
* Hematological CR (ANC count \>1.000/μL, Thrombocytes \> 100.000/μL), but MRD positivity (determined by NGS and NPM1 RT-PCR, where applicable) after any therapy except allogeneic stem cell transplantation
* Life expectancy of \> 3 months
* ECOG performance status ≤ 2
* Subject must be willing to receive transfusion of blood products
* Be willing and able to comply with the study protocol for the duration of the study
* Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and results must be negative
* Reliable contraception should be maintained throughout the study and for 6 months after study treatment
* Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods
* Males (including those who have had a vasectomy) must use an effective barrier method of contraception throughout the study and for 6 months after study treatment if sexually active with a female of childbearing potential
* All subjects must:

  * understand that the investigational product could have a potential teratogenic risk.
  * be counseled about pregnancy precautions and risks of fetal exposure.
  * be able to comply with all study-related procedures, medication use, and evaluations.

Exclusion Criteria:

The presence of ANY of the following criteria will exclude a patient from study enrollment:

* Patients proceeding to hematopoietic stem cell transplantation (suitable candidate and donor available, informed consent of patient)
* Pregnant or breast feeding females
* \>5% blasts in bone marrow or extramedullary disease
* Treatment with monoclonal antibody within 3 months before treatment with FLYSYN or known immunoglobulin intolerance
* Known positivity for HIV, active HBV, HCV, or Hepatitis A infection
* No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician and/or other physicians involved in the treatment about study participation
* No consent for biobanking
* Presence of any medical/psychiatric condition or laboratory abnormalities which may limit full compliance with the study, increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
* Prior history of malignancies, other than AML/MDS, unless the subject has been free of the disease for ≥ 2 years. Exceptions include the following: Basal cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, histological finding of prostate cancer of TNM stage T1
* Patients receiving any medication listed in the Appendix IV "Prohibited Medications" (within 14 days prior to the first dose of study drug)
* Uncontrolled infection, e.g. infection progressing under adequate antimicrobial/antifungal/antiviral treatment
* Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 14 days of screening
* Current treatment with immunosuppressive agents
* Systemic diseases (cardiovascular, renal, hepatic, etc.) that would prevent study treatment (e.g., creatinine \>1.5x upper normal serum level; bilirubin, AST or AP \>2.5x upper normal serum level; heart failure NYHA III/IV; severe obstructive or restrictive ventilation disorder)