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

NCT05737628 | Active Not Recruiting Phase 1

• 1 other identifier: BYON4228.001
• Study Type: interventional
• Target: 17
• Locations: 4 countries
• Sites: 12

Brief Summary

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

Conditions

Lymphoma

Keywords

mAB; Monoclonal antibody; Lymphoma; Non-Hodgkin's Lymphoma; SIRPα; NHL; CD20; CD47; SIRP; MCL; FL; MZL; DLBCL

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities

  Part 1

  28 days

Secondary Outcomes (1)

• Objective response rate

  2 years

Study Arms (1)

BYON4228 + Rituximab

EXPERIMENTAL

Drug: BYON4228 + Rituximab

Interventions

BYON4228 + Rituximab DRUG

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.

Also known as: Truxima

BYON4228 + Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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)

Sponsors & Collaborators

• Byondis B.V.: lead

Study Sites (12)

ASST Spedali Civili di Brescia

Brescia, Italy

Location

Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS

Candiolo, Italy

Location

Instituto Europeo di Oncologia

Milan, Italy

Location

IRCCS Ospedale San Raffaele

Milan, Italy

Location

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS IRST

Ravenna, Italy

Location

Vrije Universiteit Medisch Centrum

Amsterdam, Netherlands

Location

Radboud UMC

Nijmegen, Netherlands

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Institut Català d'Oncologia

Barcelona, Spain

Location

Centro Integral Oncológico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro

Madrid, Spain

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

University Hospitals Plymouth NHS Trust

Plymouth, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Norbert Koper

  Byondis B.V., The Netherlands

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 21, 2023
• Study Start: March 4, 2024
• Primary Completion: February 1, 2026
• Study Completion: May 1, 2026
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5); NL (2); ES (3); GB (2)