Clinical trial NCT06359002: Safety, Pharmacokinetics, and Preliminary Efficacy of BYON4413 in Acute Myeloid Leukemia and Myelodysplastic Neoplasms.
Official title: A First-in-human Dose Escalation and Expansion Trial With the Antibody-drug Conjugate BYON4413 to Evaluate Safety, Pharmacokinetics, and Preliminary Efficacy in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Neoplasms.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed / Refractory AML
Relapsed / Refractory MDS
Keywords: BYON4413
CD123
Hematologic Malignancies
Antibody Drug Conjugate
AML
MDS
Lead sponsor: Byondis B.V.
Sponsor class: INDUSTRY
First posted: 2024-04-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria details are listed here, additional requirements may apply.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (dose escalation)
timeFrame: 21 days
measure: Composite Complete Remission Rate (expansion)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Incidence and severity of adverse events
timeFrame: Up to 24 months
measure: Number of patients with dose modifications
timeFrame: Up to 24 months
measure: Rate of early death
timeFrame: Within 3 treatment cycles
measure: Maximum Plasma Concentration (Cmax) BYON4413
timeFrame: Up to 24 months
measure: Time to Cmax (Tmax) BYON4413
timeFrame: Up to 24 months
measure: Area under the curve (AUC) BYON4413
timeFrame: Up to 24 months
measure: Percentage of patients with confirmed anti-BYON4413 antibodies
timeFrame: Up to 24 months
measure: Composite Complete Remission Rate (dose escalation)
timeFrame: Up to 24 months
measure: Percentage of blasts in bone marrow change from baseline
timeFrame: Up to 24 months
measure: Percentage of blasts in peripheral blood change from baseline
timeFrame: Up to 24 months
measure: Objective response rate
timeFrame: Up to 24 months
measure: Duration of response
timeFrame: Up to 24 months
measure: Relapse-free survival
timeFrame: Up to 24 months
measure: Event-free survival
timeFrame: Up to 24 months
measure: Time to response
timeFrame: Up to 24 months
measure: Overall survival
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Het Ziekenhuisnetwerk Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
Study officials:
References: