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

NCT ID: NCT06932952

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-07
• Study Completion Date: 2026-12-31

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.

Conditions

Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BYON4228 + Pembrolizumab

Group Type: EXPERIMENTAL

BYON4228 + Pembrolizumab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Byondis B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut Jules Bordet

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

CIOCC Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

The Christie NHS Foundation Trust

Manchester, , United Kingdom

The Royal Marsden

Sutton, , United Kingdom

Countries

Belgium; Spain; United Kingdom

Other Identifiers

2024-517952-37-00

Identifier Type: CTIS

Identifier Source: secondary_id

BYON4228.002

Identifier Type: -

Identifier Source: org_study_id