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

Phase 1

Active, not recruiting

• Conditions: Solid Tumor
• Interventions: Drug: BYON3521

• Registration Number: NCT05323045
• Lead Sponsor: Byondis B.V.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2022-03-21
• Study First Submitted: 2022-03-25
• Study First Submitted QC: 2022-04-04
• Study First Posted: 2022-04-12
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-06
• Last Update Posted: 2024-06-07
• Primary Completion: 2024-07
• Study Completion: 2024-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 31

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BYON3521	BYON3521	c-MET targeting Antibody-Drug Conjugate

Primary Outcome Measures

Name	Time	Method
Incidence of dose-limiting toxicities	21 days	Part 1

Secondary Outcome Measures

Name	Time	Method
Objective response rate	21 days	Part 2

Trial Locations

Locations (4)

Istituto Europeo di Oncologia; 🇮🇹 Milan, Italy

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Radboud; 🇳🇱 Nijmegen, Netherlands

Royal Marsden; 🇬🇧 London, United Kingdom