A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate BYON3521

A First-in-human Dose-escalation and Expansion Trial With the Antibody-drug Conjugate BYON3521 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With c-MET Expressing Locally Advanced or Metastatic Solid Tumours

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05323045

Enrollment

Registered

2022-04-12

Start date

2022-03-21

Completion date

2024-09-25

Last updated

2025-07-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Solid Tumor

Keywords

ADC, c-MET, solid tumors

Brief summary

This is the first-in-human trial with BYON3521, an antibody-drug conjugate (ADC) comprising a humanized IgG1 monoclonal antibody directed against the c-MET receptor covalently conjugated to a duocarmycin-containing linker-drug.

Detailed description

This trial includes a dose-escalation part (Part 1) in which the MTD and RDE will be determined, and an expansion part (Part 2) to evaluate efficacy and safety in specific patient cohorts. BYON3521 is an ADC comprising a humanized IgG1 monoclonal antibody (mAb) directed against the c-MET receptor covalently and site-specifically conjugated to a duocarmycin-containing linkerdrug.

Interventions

DRUGBYON3521

BYON3521 (in the vein) infusion every three weeks. Number of cycles: until cancer progression or unacceptable toxicity develops. Different doses.

Study design

Allocation

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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 tumours of any origin; * Part 2 (expansion): * Cohort A: Non-squamous non small cell lung cancer (non-squamous NSCLC); * Cohort B: Gynaecological cancers: ovarian cancer, endometrial cancer, cervical cancer; * Cohort C: Pancreatic adenocarcinoma (PA); * Cohort D: Uveal melanoma (UM). * c-MET prevalence confirmed by: * Part 1: Tumour c-MET positive membrane staining by immunohistochemistry (IHC) and/or MET amplification by dual In Situ Hybridization (dISH) and/or known MET-mutation; * Part 2: Tumour c-MET membrane expression by immunohistochemistry (IHC score ≥ 2+) as determined by the central laboratory on most recent available/obtained tumour material from a site not previously irradiated; * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1; * Adequate organ function

Exclusion criteria

* Having been treated with: * Trastuzumab duocarmazine (SYD985) at any time; * Other anticancer therapy within 4 weeks or as defined in the protocol; * History or presence of keratitis, glomerulonephritis, idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan; * 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

Design outcomes

Primary

Measure	Time frame	Description
Incidence of dose-limiting toxicities	21 days	Part 1

Secondary

Measure	Time frame	Description
Objective response rate	21 days	Part 2

Countries

Belgium, Italy, Netherlands, United Kingdom

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 9, 2026