Lymphoma
Conditions
Keywords
mAB, Monoclonal antibody, Lymphoma, Non-Hodgkin's Lymphoma, SIRPα, NHL, CD20, CD47, SIRP, MCL, FL, MZL, DLBCL
Brief summary
This is the first-in-human study with BYON4228, a humanized monoclonal antibody (mAb) directed against SIRPα.
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.
Interventions
DRUGBYON4228 + 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.
Sponsors
Byondis B.V.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicities | 28 days | Part 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | 2 years | Part 2 |
Countries
Italy, Netherlands, Spain, United Kingdom
Contacts
STUDY_DIRECTORNorbert Koper
Byondis B.V., The Netherlands
Outcome results
None listed