First use of BYON4228, a monoclonal antibody for lymphoma treatment

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 study is testing a new treatment called BYON4228 to see if it can help people with relapsed or hard-to-treat non-Hodgkin's lymphoma by boosting their immune response against cancer cells.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Byondis B.V. (Industry-sponsored)
• Drugs / interventions: rituximab
• Locations: 12 sites (Brescia and 11 other locations)
• Trial ID: NCT05737628 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates BYON4228, a humanized monoclonal antibody targeting SIRPα, in patients with relapsed or refractory non-Hodgkin's lymphoma. The study consists of two parts: a dose escalation phase to determine the maximum tolerated dose and a subsequent expansion phase to assess the efficacy and safety of the treatment in specific patient cohorts. BYON4228 works by blocking the interaction between SIRPα and CD47, potentially enhancing the immune response against cancer cells.

Who should consider this trial

Good fit: Ideal candidates include adults with relapsed or refractory B-cell non-Hodgkin's lymphoma expressing CD20 after multiple lines of therapy.

Not a fit: Patients who have previously been treated with CD47 or SIRPα targeting agents may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat lymphomas.

How similar studies have performed: While this approach is novel, similar monoclonal antibody therapies have shown promise in treating various cancers.

Eligibility criteria

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)

Where this trial is running

Brescia and 11 other locations

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

Study contacts

• Study coordinator: Willem Klaassen

Conditions Lymphoma; mAB; Monoclonal antibody; Non-Hodgkin's Lymphoma; SIRPα; NHL; CD20; CD47