A first patient has been dosed in a Phase 1 dose escalation and expansion study of the SIRPα-directed monoclonal antibody BYON4228 in patients with advanced or metastatic solid tumors.
BYON4228, being developed by Netherlands-based Byondis*, is part of the next generation immuno-oncology (IO) program that targets and blocks the CD47-signal-regulatory protein (SIRP)α axis, responsible for tumors’ ability to escape from recognition and destruction by the immune system.[1]
Selective targeting
By targeting SIRPα and not CD47, BYON4228 offers selective targeting of myeloid cells and avoids disruption of other biologically meaningful CD47-dependent interactions. In preclinical studies, BYON4228 was found to potentiate the tumor killing capacity of tumor-targeting mAbs tested without the toxicity associated with CD47 agents.[1]
Based on preclinical studies, BYON4228 is a highly differentiating pan-allelic SIRPα antibody without T-cell SIRPγ recognition that promotes the destruction of antibody-opsonized cancer cells.[1]
Trial design
The clinical trial is designed to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of BYON4228 alone and in combination with pembrolizumab (Keytruda®; Merck & Co/MSD), a PD-1 inhibitor, in patients with advanced or metastatic solid tumors.
Part 1 of the BYON4228.002 trial will evaluate the safety of BYON4228 alone and in combination to determine the maximum tolerated dose (MTD), or optimal biological dose (OBD) if the MTD is not reached, and recommended combination dose regimen(s) for expansion (RDEs).
The second part of the trial will evaluate the objective tumor response rate (ORR). The secondary objectives of this trial are safety, pharmacokinetics, immunogenicity and preliminary efficacy. The trial will be conducted at multiple sites across Europe, including the United Kingdom, Belgium and Spain.
“Building on strong preclinical data, we believe that there is broad potential for BYON4228 alone and in combination with tumor-targeting antibodies, checkpoint inhibitors and antibody-drug conjugates (ADC) and other modalities across hematological and solid tumors,” said Louis Denis, MD, Chief Medical Officer, Byondis.
“We look forward to evaluating the results of this trial to support the clinical development of BYON4228 alone and in combination with other agents and to bring a new therapeutic option to patients with high unmet medical need.”
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Note:* Byondis is a sponsor of ADC Review | J. Antibody-drug Conjugates. See: Byondis: A Passion for Patients and Precision Medicines. [Link]
Clinical trials
First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 – ClinicalTrials.gov ID NCT05737628
A Dose Escalation and Expansion Trial With BYON4228 Alone and in Combination in Patients With Advanced or Metastatic Solid Tumors
ClinicalTrials.gov ID NCT06932952
Highlights of prescribing information
Pembrolizumab (Keytruda®; Merck & Co/MSD)[Prescribing Information]
Reference
[1] van Helden MJ, Zwarthoff SA, Arends RJ, Reinieren-Beeren IMJ, Paradé MCBC, Driessen-Engels L, de Laat-Arts K, Damming D, Santegoeds-Lenssen EWH, van Kuppeveld DWJ, Lodewijks I, Olsman H, Matlung HL, Franke K, Mattaar-Hepp E, Stokman MEM, de Wit B, Glaudemans DHRF, van Wijk DEJW, Joosten-Stoffels L, Schouten J, Boersema PJ, van der Vleuten M, Sanderink JWH, Kappers WA, van den Dobbelsteen D, Timmers M, Ubink R, Rouwendal GJA, Verheijden G, van der Lee MMC, Dokter WHA, van den Berg TK. BYON4228 is a pan-allelic antagonistic SIRPα antibody that potentiates destruction of antibody-opsonized tumor cells and lacks binding to SIRPγ on T cells. J Immunother Cancer. 2023 Apr;11(4):e006567. doi: 10.1136/jitc-2022-006567. PMID: 37068796; PMCID: PMC10186489.
Featured image courtesy: © 2020 – 2025 Byondis. Used with permission
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