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Trial record 1 of 1 for:    BYON4228.001
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First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228

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

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
Estimated 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)
Actual Study Start Date : March 4, 2024
Estimated Primary Completion Date : October 1, 2024
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arms and Interventions
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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 Name: Truxima


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of dose-limiting toxicities [ Time Frame: 28 days ]
    Part 1


Secondary Outcome Measures :
  1. Objective response rate [ Time Frame: 2 years ]
    Part 2


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05737628


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

Locations
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Italy
ASST Spedali Civili di Brescia Recruiting
Brescia, Italy
Contact: Dr. A. Re         
Netherlands
Amsterdam Universitair Medisch Centrum locatie VUmc Recruiting
Amsterdam, Netherlands
Contact: Dr. M. Chamuleau         
Radboud UMC Recruiting
Nijmegen, Netherlands
Contact: Dr. W. Stevens         
Spain
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Dr. F. Bosch Albareda         
Institut Català d'Oncologia Recruiting
Barcelona, Spain
Contact: Dr. E. Gonzalez Barca         
Centro Integral Oncológico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro Recruiting
Madrid, Spain
Contact: Dr. J. Perez De Oteyza         
United Kingdom
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom
Contact: Dr. K. Linton         
Derriford Hospital Recruiting
Plymouth, United Kingdom
Contact: Dr. D. Lewis         
Sponsors and Collaborators
Byondis B.V.
Investigators
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Study Director: Willem Klaassen Byondis B.V., The Netherlands
More Information
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Responsible Party: Byondis B.V.
ClinicalTrials.gov Identifier: NCT05737628    
Other Study ID Numbers: BYON4228.001
First Posted: February 21, 2023    Key Record Dates
Last Update Posted: March 20, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Byondis B.V.:
mAB
Monoclonal antibody
Lymphoma
Non-Hodgkin's Lymphoma
SIRPα
NHL
CD20
 CD47
SIRP
MCL
FL
MZL
DLBCL
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
 Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents