Clinical trial NCT05737628: First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lymphoma
Keywords: mAB
Monoclonal antibody
Lymphoma
Non-Hodgkin's Lymphoma
SIRPα
NHL
CD20
CD47
SIRP
MCL
FL
MZL
DLBCL
Lead sponsor: Byondis B.V.
Sponsor class: INDUSTRY
First posted: 2023-02-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Incidence of dose-limiting toxicities
timeFrame: 28 days
Secondary outcomes:
measure: Objective response rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Candiolo
country: Italy
facility: Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS
city: Milan
country: Italy
facility: Instituto Europeo di Oncologia
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Ravenna
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS IRST
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
Study officials:
affiliation: Byondis B.V., The Netherlands
name: Willem Klaassen
role: STUDY_DIRECTOR
References: