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

Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05737628
• Other study ID #: BYON4228.001
• Status: Recruiting
• Phase: Phase 1
• Start date: March 4, 2024
• Est. completion date: December 1, 2025

Study information

• Verified date: March 2024
• Source: Byondis B.V.
• Contact: Willem Klaassen
• Phone: +31 (0)24 679 5100
• Email: clinicaltrials[@]byondis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 1, 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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 SIRPa 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)

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• BYON4228 + Rituximab
20 mg/mL BYON4228 in 8 mL solution for infusion. Rituximab 500 mg concentrate for solution for infusion.

Locations

Country	Name	City	State
Italy	ASST Spedali Civili di Brescia	Brescia
Netherlands	Amsterdam Universitair Medisch Centrum locatie VUmc	Amsterdam
Netherlands	Radboud UMC	Nijmegen
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Català d'Oncologia	Barcelona
Spain	Centro Integral Oncológico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro	Madrid
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Derriford Hospital	Plymouth

Sponsors (1)

Lead Sponsor	Collaborator
Byondis B.V.

Countries where clinical trial is conducted

Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities	Part 1	28 days
Secondary	Objective response rate	Part 2	2 years