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

Sponsor

Byondis B.V. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05737628

Collaborator

(none)

100

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: BYON4228 + Rituximab	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BYON4228 + Rituximab BYON4228 is a humanized monoclonal antibody (mAb) directed against SIRPα. BYON4228 IV infusion every four weeks. Number of cycles: until cancer progression or unacceptable toxicity develops. Different doses. Rituximab IV infusion (375 mg/m2) starts after first BYON4228 cycle. Weekly infusion during the first cycle and every four weeks in subsequent 5 cycles.	Drug: BYON4228 + Rituximab 20 mg/mL BYON4228 in 8 mL solution for infusion. Rituximab 500 mg concentrate for solution for infusion. Other Names: Truxima

Arm

Intervention/Treatment

Experimental: BYON4228 + Rituximab

BYON4228 is a humanized monoclonal antibody (mAb) directed against SIRPα. BYON4228 IV infusion every four weeks. Number of cycles: until cancer progression or unacceptable toxicity develops. Different doses. Rituximab IV infusion (375 mg/m2) starts after first BYON4228 cycle. Weekly infusion during the first cycle and every four weeks in subsequent 5 cycles.

Drug: BYON4228 + Rituximab

20 mg/mL BYON4228 in 8 mL solution for infusion. Rituximab 500 mg concentrate for solution for infusion.

Other Names:

Truxima

Outcome Measures

Primary Outcome Measures

Incidence of dose-limiting toxicities [28 days]
Part 1

Secondary Outcome Measures

Objective response rate [2 years]
Part 2

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 or autologous CAR-T cell therapy.
Part 2 (dose expansion):

Histologically confirmed diffuse large B-cell lymphoma (DLBCL) expressing CD20 by IHC or flow cytometry, R/R to frontline therapy; or R/R to second line salvage regimens or autologous hematopoietic cell transplantation or autologous CAR-T cell therapy.
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 or autologous CAR-T cell therapy.

Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
Adequate organ function

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;
Symptomatic brain metastases, brain metastases requiring steroids or treatment for brain metastases within 8 weeks
Severe active infection or other severe uncontrolled systemic disease (e.g. advanced renal disease, pulmonary, uncontrolled diabetes mellitus, severely immunocompromised state, or metabolic disease)