Relapsed / Refractory AML, Relapsed / Refractory MDS
Conditions
Keywords
BYON4413, CD123, Hematologic Malignancies, Antibody Drug Conjugate, AML, MDS
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.
Interventions
DRUGBYON4413
BYON4413 will be administered by IV infusion.
Sponsors
Byondis B.V.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time to response | Up to 24 months | — |
| Overall survival | Up to 24 months | — |
| Incidence and severity of adverse events | Up to 24 months | — |
| Number of patients with dose modifications | Up to 24 months | — |
| Rate of early death | Within 3 treatment cycles | — |
| Maximum Plasma Concentration (Cmax) BYON4413 | Up to 24 months | — |
| Time to Cmax (Tmax) BYON4413 | Up to 24 months | — |
| Area under the curve (AUC) BYON4413 | Up to 24 months | — |
| Percentage of patients with confirmed anti-BYON4413 antibodies | Up to 24 months | — |
| Composite Complete Remission Rate (dose escalation) | Up to 24 months | CR + CRh + CRi according ELN 2022 criteria |
| Percentage of blasts in bone marrow change from baseline | Up to 24 months | — |
| Percentage of blasts in peripheral blood change from baseline | Up to 24 months | — |
| Objective response rate | Up to 24 months | CR + CRh + CRi + MLFS + PR according ELN 2022 criteria |
| Relapse-free survival | Up to 24 months | — |
| Duration of response | Up to 24 months | — |
| Event-free survival | Up to 24 months | — |
Countries
Belgium, Netherlands, Spain
Outcome results
None listed