A Dose Escalation and Expansion Trial With BYON4228 Alone and in Combination in Patients With Advanced or Metastatic Solid Tumors

A Dose Escalation and Expansion Trial With the SIRPα-directed Monoclonal Antibody BYON4228 Alone and in Combination to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy in Patients With Advanced or Metastatic Solid Tumors

This is a phase I trial with BYON4228, a humanized monoclonal antibody (mAb) directed against signal regulatory protein (SIRP)α in solid tumors, alone and in combination with pembrolizumab.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: BYON4228 + Pembrolizumab

Detailed Description

This study includes a dose escalation part (Part 1) in which the MTD or OBD and RDE(s) will be determined. This trial includes an expansion part (Part 2) to evaluate efficacy and safety of BYON4228 in combination with pembrolizumab 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
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Institut Jules Bordet
  • Leuven, Belgium
    • UZ Leuven
• Spain
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Díaz
  • Madrid, Spain
    • CIOCC Hospital Universitario HM Sanchinarro
• United Kingdom
  • Manchester, United Kingdom
    • The Christie NHS Foundation Trust
  • Sutton, United Kingdom
    • The Royal Marsden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with histologically confirmed, locally advanced or metastatic cancer who has progressed on standard therapy or for whom no standard therapy exists:

  • Part 1 (dose escalation): Solid tumors of any origin;
  • Part 2 (expansion): Patients with other solid tumor types indicated for pembrolizumab monotherapy;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
• For Part 2 only: at least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumors (RECIST version 1.1);
• Adequate baseline organ function.

Exclusion Criteria:

• Having been treated with CD47 or SIRPα targeting agents or other anticancer therapy within 4 weeks prior to the start of IMP treatment;
• History of hypersensitivity or allergic reaction to any of the excipients of BYON4228;
• Any contraindication to pembrolizumab treatment;
• For Part 2: Patients previously given a PD-1 or PD-L1 inhibitor who had subsequent disease progression within 8 weeks of initiation;
• Symptomatic brain metastases;
• History of autoimmune disorders;
• Severe active infection or other severe uncontrolled systemic disease;
• Having clinically significant cardiovascular disease;
• Known infection of Hepatitis B, C or E.

Key inclusion and exclusion criteria details are listed here, additional requirements may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BYON4228 + Pembrolizumab	Drug: BYON4228 + Pembrolizumab; BYON4228 is a humanized monoclonal antibody (mAb) directed against SIRPα. BYON4228 IV infusion every three weeks until disease progression or unacceptable toxicity. Different doses. Pembrolizumab IV infusion (200 mg) every three weeks from the second treatment cycle onwards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicities		21 days
Objective Response Rate	Part 2 (expansion): To evaluate the objective tumor response rate (ORR).	2 years

Collaborators and Investigators

• Sponsor: Byondis B.V.

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 10, 2025
• First Submitted That Met QC Criteria: April 10, 2025
• First Posted (Actual): April 17, 2025

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Monoclonal antibody; CD47; SIRPα; mAB; SIRP
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: BYON4228.002; 2024-517952-37-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No