Active, not recruiting
Phase 1
First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228
Condition(s) studied
Lymphoma
Investigational drug(s) / intervention(s)
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
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)
| Facility | City | Region | Status |
| 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 |
|
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