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

• ClinicalTrials.gov Identifier: NCT05737628
• Recruitment Status: Recruiting
• First Posted: February 21, 2023
• Last Update Posted: March 20, 2024
• Sponsor: Byondis B.V.
• Information provided by (Responsible Party): Byondis B.V.

Tracking Information

• First Submitted Date: February 8, 2023
• First Posted Date: February 21, 2023
• Last Update Posted Date: March 20, 2024
• Actual Study Start Date: March 4, 2024
• Estimated Primary Completion Date: October 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 20, 2023)

Incidence of dose-limiting toxicities [ Time Frame: 28 days ]

Part 1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 20, 2023)

Objective response rate [ Time Frame: 2 years ]

Part 2

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

Drug: BYON4228 + Rituximab

20 mg/mL BYON4228 in 8 mL solution for infusion.

Rituximab 500 mg concentrate for solution for infusion.

Other Name: Truxima

Study Arms

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.

Intervention: Drug: BYON4228 + Rituximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 20, 2023): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2025
• Estimated Primary Completion Date: October 1, 2024 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Willem Klaassen; +31 (0)24 679 5100; clinicaltrials@byondis.com

• Listed Location Countries: Italy, Netherlands, Spain, United Kingdom

Administrative Information

• NCT Number: NCT05737628
• Other Study ID Numbers: BYON4228.001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Byondis B.V.
• Original Responsible Party: Same as current
• Current Study Sponsor: Byondis B.V.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Willem Klaassen; Byondis B.V., The Netherlands

• PRS Account: Byondis B.V.
• Verification Date: March 2024