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Active, not recruiting Phase 1

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

NCT05737628 · tracked via the Priya Life Science Italy tracker
Phase
Phase 1
Started
2024-03-04
Last updated
2026-01-16

Condition(s) studied

Lymphoma

Investigational drug(s) / intervention(s)

BYON4228 + RituximabAll BYON4228 trials (2) →All Rituximab trials (253) →

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.

Study summary

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

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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)

Primary outcome measure(s)

  • Incidence of dose-limiting toxicities — 28 days
    Part 1

Trial sites (12)

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

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05737628 on ClinicalTrials.gov ↗ ← All trials in Italy