LymphomaPhase 1NCT05737628
First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228
A Phase 1 study testing BYON4228 + Rituximab in people with Lymphoma, run by Byondis B.V. at 12 sites in 4 countries.
Trial summary
This is the first-in-human study with BYON4228, a humanized monoclonal antibody (mAb) directed against SIRPα. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- BYON4228 + Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 12 sitesin 4 countries
- Study dates
- 4 Mar 2024to May 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
- 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.
- 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;
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- 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;
Who cannot join
- 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;
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- 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)
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
Italy5 sites
ASST Spedali Civili di Brescia
Brescia
Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS
Candiolo
Instituto Europeo di Oncologia
Milan
IRCCS Ospedale San Raffaele
Milan
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS IRST
Ravenna
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona
Institut Català d'Oncologia
Barcelona
Centro Integral Oncológico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro
Madrid
Netherlands2 sites
Vrije Universiteit Medisch Centrum
Amsterdam
Radboud UMC
Nijmegen
United Kingdom2 sites
The Christie NHS Foundation Trust
Manchester
University Hospitals Plymouth NHS Trust
Plymouth
About this study
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)
This is the first-in-human study with BYON4228, a humanized monoclonal antibody (mAb) directed against SIRPα.
Read the 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.
- Conditions
- Lymphoma
- Being tested
- BYON4228 + Rituximab
- Keywords
- mAB, Monoclonal antibody, Lymphoma, Non-Hodgkin's Lymphoma, SIRPα, NHL, CD20, CD47, SIRP, MCL, FL, MZL, DLBCL
- Medical subject headings
- Lymphoma, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BYON4228 + RituximabDrug
Also called Truxima
BYON4228 is a humanized monoclonal antibody (mAb) directed against SIRPα. BYON4228 IV infusion every four weeks until disease progression or unacceptable toxicity. Different doses.
Rituximab IV infusion (375 mg/m2) starting from the second treatment cycle onwards. Weekly infusion during the first cycle and every four weeks in subsequent 5 cycles.
| Study group | Role | What they receive |
|---|---|---|
| BYON4228 + Rituximab | Experimental | Not described Receives: Drug: BYON4228 + Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities
Part 1
Measured: 28 days
Secondary outcomes (1)
Objective response rate
Part 2
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start4 Mar 2024
- Primary completionFeb 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Byondis B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Norbert Koper, Study director, Byondis B.V., The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05737628
- Sponsor's protocol ID
- BYON4228.001
- Status last verified
- Jan 2026
- First submitted
- 8 Feb 2023
- Last updated
- 16 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05737628
- Acronym / sponsor ID
- BYON4228.001
- Conditions
- Lymphoma
- Keywords
- mAB, Monoclonal antibody, Lymphoma, Non-Hodgkin's Lymphoma, SIRPα, NHL, CD20, CD47
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Byondis B.V.Industry (pharma, biotech, devices)
- Study start
- 4 Mar 2024 (actual)
- Primary completion
- Feb 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 21 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BYON4228 + Rituximab | Experimental | Drug: BYON4228 + Rituximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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):
- 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.
- 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;
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BYON4228 + RituximabAlso: TruximaBYON4228 is a humanized monoclonal antibody (mAb) directed against SIRPα. BYON4228 IV infusion every four weeks until disease progression or unacceptable toxicity. Different doses. Rituximab IV infusion (375 mg/m2) starting from the second treatment cycle onwards. Weekly infusion during the first cycle and every four weeks in subsequent 5 cycles. | Drug | BYON4228 + Rituximab |
Primary outcome
Incidence of dose-limiting toxicities
Time frame: 28 days
Part 1
1 secondary outcome
Objective response rate
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Norbert Koper study director
Byondis B.V., The Netherlands
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BYON4228 + Rituximab in people with Lymphoma, run by Byondis B.V. at 12 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Italy, Spain, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2026.