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

Phase 1

Not yet recruiting

• Conditions: Solid Tumor
• Interventions: Drug: BYON4228; Combination Product: Pembrolizumab

• Registration Number: NCT06932952
• Lead Sponsor: Byondis B.V.

Brief Summary

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.

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 Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-10
• Study First Submitted QC: 2025-04-10
• Study First Posted: 2025-04-17
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-22
• Study Start: 2025-05
• Primary Completion: 2027-05
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 85

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BYON4228 + Pembrolizumab	BYON4228	-
BYON4228 + Pembrolizumab	Pembrolizumab	-

Primary Outcome Measures

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