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

NCT05323045 | Completed Phase 1

• 1 other identifier: BYON3521.001
• Study Type: interventional
• Target: 31
• Locations: 4 countries
• Sites: 4

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.

Conditions

Solid Tumor

Keywords

ADC; c-MET; solid tumors

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities

  Part 1

  21 days

Secondary Outcomes (1)

• Objective response rate

  21 days

Study Arms (1)

BYON3521

EXPERIMENTAL

c-MET targeting Antibody-Drug Conjugate

Drug: BYON3521

Interventions

BYON3521 DRUG

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

BYON3521

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Byondis B.V.: lead

Study Sites (4)

Institut Jules Bordet

Brussels, Belgium

Location

Istituto Europeo di Oncologia

Milan, 1070, Italy

Location

Radboud

Nijmegen, 6500HB, Netherlands

Location

Royal Marsden

London, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Groothuis PG, Jacobs DCH, Hermens IAT, Damming D, Berentsen K, Mattaar-Hepp E, Stokman MEM, Boekel TV, Rouwette M, van der Vleuten MAJ, Sesink A, Dijcks FA, Coumans RGE, Schouten J, Glaudemans DH, Wijk DV, Blomenrohr M, Kappers WA, Ubink R, van der Lee MMC, Dokter WHA. Preclinical Profile of BYON3521 Predicts an Effective and Safe MET Antibody-Drug Conjugate. Mol Cancer Ther. 2023 Jun 1;22(6):765-777. doi: 10.1158/1535-7163.MCT-22-0596.

  PMID: 37042205 DERIVED

Study Officials

• Tanya Vermaas

  Byondis B.V., The Netherlands

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2022
• First Posted: April 12, 2022
• Study Start: March 21, 2022
• Primary Completion: March 4, 2024
• Study Completion: September 25, 2024
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); IT (1); NL (1); GB (1)