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Safety, Pharmacokinetics, and Preliminary Efficacy of BYON4413 in Acute Myeloid Leukemia and Myelodysplastic Neoplasms.

Phase 1
Recruiting
Conditions
Relapsed / Refractory MDS
Relapsed / Refractory AML
Interventions
Drug: BYON4413
Registration Number
NCT06359002
Lead Sponsor
Byondis B.V.
Brief Summary

This is the first-in-human trial with BYON4413 to evaluate safety, PK, immunogenicity, and anti-leukemia activity of BYON4413 in patients with AML or MDS.

Detailed Description

This trial includes two parts. Part 1 is a dose escalation study in which the maximum tolerated dose and recommended dose for expansion of BYON4413 will be determined. Part 2 is an expansion study to evaluate the anti-leukemia activity and safety of BYON4413.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
Inclusion Criteria
  • Patients who have progressed on standard therapy or have no established alternative treatment, with a diagnosis of:

    • R/R AML (WHO 2022) OR
    • MDS (WHO 2022) with ≥10% blasts in BM and have received ≥3 cycles of HMA
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2;

  • Adequate baseline organ function.

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Exclusion Criteria
  • Having been treated with any CD123-targeting therapies;
  • Having received allogeneic hematopoietic stem cell transplantation within 100 days prior to start Cycle 1 Day 1;
  • Having treatment-related toxicities from prior anti-leukemia therapies that have not resolved to CTCAE Grade ≤ 1;
  • Having active central nervous system AML or AML of the APL/M3 subtype;
  • History of keratitis;
  • History of specified lung or renal disease;
  • Having clinically significant cardiovascular disease;
  • Known infection of Hepatitis B, C or E.

Key inclusion and exclusion criteria details are listed here, additional requirements may apply.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose EscalationBYON4413Escalating dose cohorts of BYON4413 for patients with AML or MDS.
Primary Outcome Measures
NameTimeMethod
Incidence of dose-limiting toxicities (dose escalation)21 days
Composite Complete Remission Rate (expansion)Up to 24 months

CR + CRh + CRi according ELN 2022 criteria

Secondary Outcome Measures
NameTimeMethod
Incidence and severity of adverse eventsUp to 24 months
Relapse-free survivalUp to 24 months
Maximum Plasma Concentration (Cmax) BYON4413Up to 24 months
Percentage of blasts in bone marrow change from baselineUp to 24 months
Number of patients with dose modificationsUp to 24 months
Time to Cmax (Tmax) BYON4413Up to 24 months
Percentage of patients with confirmed anti-BYON4413 antibodiesUp to 24 months
Objective response rateUp to 24 months

CR + CRh + CRi + MLFS + PR according ELN 2022 criteria

Time to responseUp to 24 months
Overall survivalUp to 24 months
Percentage of blasts in peripheral blood change from baselineUp to 24 months
Event-free survivalUp to 24 months
Rate of early deathWithin 3 treatment cycles
Area under the curve (AUC) BYON4413Up to 24 months
Composite Complete Remission Rate (dose escalation)Up to 24 months

CR + CRh + CRi according ELN 2022 criteria

Duration of responseUp to 24 months

Trial Locations

Locations (9)

Het Ziekenhuisnetwerk Antwerpen

🇧🇪

Antwerpen, Belgium

UZ Leuven

🇧🇪

Leuven, Belgium

Universitair Medisch Centrum Groningen

🇳🇱

Groningen, Netherlands

Institut Catala d'Oncologia

🇪🇸

Badalona, Spain

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

Hospital de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Hospital San Pedro de Alcantara

🇪🇸

Caceres, Spain

Hospital Universitario de Salamanca

🇪🇸

Salamanca, Spain

Hospital Universitario y Politecnico La Fe

🇪🇸

Valencia, Spain

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