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)

Study Identifier:
BYON4228-002
CT.gov Identifier:
NCT05737628
EudraCT Identifier:
2022-002018-18
EU Trial (CTIS) Number:
2024-512390-27-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

To evaluate BYON4228 in patients with cancer

To evaluate efficacy and safety in specific patient cohorts

Part 1 (dose escalation) evaluates the safety, tolerability and Pharmacokinetics (PK) of, and receptor occupancy by BYON4228 to determine the maximum tolerated dose (MTD) or optimal biological dose (OBD) if the MTD is not reached, and recommended dose for expansion (RDE)

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Lymphoma
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Patients will receive BYON4228.
    • Read More
  • Drug: Experimental: BYON4228 + RituximabDrug: BYON4228 + Rituximab
  • Drug: 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: A 28-day flat dose escalation schedule starting at 7 mg will be followed in a standard 3+3 design. Notably, only 1 cycle BYON4228 monotherapy will be given in each patient before combining with rituximab (375 mg/m2 first cycle weekly administration; thereafter every 4 weeks for a total of 6 cycles). In part 2 (cohort expansion) BYON4228 + rituximab combination therapy will be given from cycle 1 onwards to further evaluate safety and efficacy in up to 24 additional diffuse large B cell lymphoma (DLBCL) patients and up to 24 patients with either marginal zone lymphoma (MZL) or follicular lymphoma (FL).
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    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):
    • A. 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.
    • 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 or autologous CAR-T cell therapy.
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
    • Adequate organ function
    • inclusion criteria include, for part 1: B-cell NHL expressing CD20 by immunohistochemistry (IHC) or flow cytometry, R/R to at least 2 prior lines of therapy; for part 2, cohort A: Histologically confirmed DLBCL expressing CD20 R/R to front-line therapy, or second-line salvage regimens; for part 2, cohort B: Histologically confirmed MZL or FL (Grade 1-3a) expressing CD20, R/R to at least 2 prior lines of therapy. Autologous or allogeneic hematopoietic cell transplantation and autologous CAR-T cell therapy are allowed as prior lines.
    Exclusion criteria
    • Having been treated with CD47 or SIRP 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)
    • exclusion criteria include prior treatment with CD47- or SIRP- targeting agents at any time; other anticancer therapy including investigational agents within 2 weeks or within at least 4 times the elimination half-life; Burkitt’s lymphoma; history of active auto-immune disorders, active infections or uncontrolled systemic disease. Tumor response is determined according to Lugano and LYRIC criteria.

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Emiliano Calvo
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Lymphoma
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Bernard Doger de Speville
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Lymphoma