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

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed / Refractory AML; Relapsed / Refractory MDS
• Intervention / Treatment: Drug: BYON4413

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Glenn van Wigcheren; Phone Number: +31 24 679 5100; Email: clinicaltrials@byondis.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Escalating dose cohorts of BYON4413 for patients with AML or MDS.	Drug: BYON4413; BYON4413 will be administered by IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities (dose escalation)		21 days
Composite Complete Remission Rate (expansion)	CR + CRh + CRi according ELN 2022 criteria	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to response		Up to 24 months
Duration of 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)	CR + CRh + CRi according ELN 2022 criteria	Up to 24 months
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	CR + CRh + CRi + MLFS + PR according ELN 2022 criteria	Up to 24 months
Relapse-free survival		Up to 24 months
Event-free survival		Up to 24 months

Collaborators and Investigators

• Sponsor: Byondis B.V.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 26, 2024
• First Submitted That Met QC Criteria: April 5, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: AML; MDS; Hematologic Malignancies; Antibody Drug Conjugate; CD123; BYON4413
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Leukemia; Leukemia, Myeloid; Neoplasms; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Preleukemia
• Other Study ID Numbers: BYON4413.001; 2023-507781-13-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No