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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: BYON3521


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BYON3521<br>c-MET targeting Antibody-Drug Conjugate | Drug: BYON3521<br>* BYON3521 (in the vein) infusion every three weeks. Number of cycles: until cancer progression or unacceptable toxicity develops. Different doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities | Part 1 | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Part 2 | 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADC, c-MET, solid tumors