First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228

January 15, 2026 updated by: Byondis B.V.

First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 Alone and in Combination With Rituximab to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy in Patients With Relapsed/Refractory CD20 Positive B-cell Non-Hodgkin's Lymphoma (NHL)

This is the first-in-human study with BYON4228, a humanized monoclonal antibody (mAb) directed against SIRPα.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This study includes a dose escalation part (Part 1) in which the MTD and dose regimen for expansion (RDE) will be determined, and an expansion part (Part 2) to evaluate efficacy and safety in specific patient cohorts.

BYON4228 is a humanized IgG1 mAb directed against SIRPα. BYON4228 binds SIRPα expressed on innate immune cells, especially monocytes, macrophages and neutrophils. BYON4228 blocks binding of SIRPα to CD47 and inhibits signaling through the CD47-SIRPα axis.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Brescia, Italy
        • ASST Spedali Civili di Brescia
      • Candiolo, Italy
        • Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS
      • Milan, Italy
        • Irccs Ospedale San Raffaele
      • Milan, Italy
        • Instituto Europeo di Oncologia
      • Ravenna, Italy
        • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS IRST
  • Netherlands
      • Amsterdam, Netherlands
        • Vrije Universiteit Medisch Centrum
      • Nijmegen, Netherlands
        • Radboud UMC
  • Spain
      • Barcelona, Spain
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain
        • Institut Catala d'Oncologia
      • Madrid, Spain
        • Centro Integral Oncológico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro
  • United Kingdom
      • Manchester, United Kingdom
        • The Christie NHS Foundation Trust
      • Plymouth, United Kingdom
        • University Hospitals Plymouth NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Part 1 (dose escalation): B-cell NHL expressing CD20 by immunohistochemistry (IHC) or flow cytometry, relapsed/refractory (R/R) to at least 2 prior lines of therapy.
  • Part 2 (dose expansion):

A. Histologically confirmed diffuse large B-cell lymphoma (DLBCL) or Mantle Cell Lymphoma (MCL) expressing CD20 by IHC or flow cytometry, R/R to frontline therapy.

B. Histologically confirmed marginal zone or follicular lymphoma (Grade 1-3a) expressing CD20 by IHC or flow cytometry, R/R to at least 2 prior lines of therapy.

  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
  • Adequate organ function;

  • Laboratory measurements, blood counts (Growth Factor (GF) support and blood transfusions are not allowed within 2 weeks prior to this assessment):

    • Hemoglobin ≥ 8.5 g/dL (> 5.28 mmol/L);
    • Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/mL;
    • Platelet counts ≥ 50 × 10^9/mL;

Exclusion Criteria:

  • Having been treated with CD47 or SIRPα targeting agents at any time or other anticancer therapy within 4 weeks or as defined in the protocol;
  • History of hypersensitivity or allergic reaction to any of the excipients of BYON4228 or rituximab which led to permanent discontinuation of the treatment;
  • Burkitt's lymphoma;
  • Red blood cell (RBC) transfusion dependence;
  • Patients with active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD;
  • History of autoimmune hemolytic anemia or autoimmune thrombocytopenia;
  • History of active autoimmune disorders (including but not limited to: Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) or other conditions that compromise or impair the immune system (except for hypogammaglobulinemia);
  • History (within 6 months prior to start IMP) or presence of clinically significant cardiovascular disease such as unstable angina, congestive heart failure, myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication;
  • Currently diagnosed or suspected CNS involvement;
  • Severe active infection or other severe uncontrolled systemic disease (e.g. advanced renal disease, pulmonary, uncontrolled diabetes mellitus, severely immunocompromised state, or metabolic disease)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BYON4228 + Rituximab
Drug: BYON4228 + Rituximab

BYON4228 is a humanized monoclonal antibody (mAb) directed against SIRPα. BYON4228 IV infusion every four weeks until disease progression or unacceptable toxicity. Different doses.

Rituximab IV infusion (375 mg/m2) starting from the second treatment cycle onwards. Weekly infusion during the first cycle and every four weeks in subsequent 5 cycles.

Other Names:
  • Truxima

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicities
Time Frame: 28 days
Part 1
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: 2 years
Part 2
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Byondis B.V.

Investigators

  • Study Director: Norbert Koper, Byondis B.V., The Netherlands

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2024

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

May 1, 2026

Study Registration Dates

First Submitted

February 8, 2023

First Submitted That Met QC Criteria

February 20, 2023

First Posted (Actual)

February 21, 2023

Study Record Updates

Last Update Posted (Estimated)

January 16, 2026

Last Update Submitted That Met QC Criteria

January 15, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BYON4228.001

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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