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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05323045
• Other study ID #: BYON3521.001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 21, 2022
• Est. completion date: July 2024

Study information

• Verified date: June 2024
• Source: Byondis B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumor

Intervention

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

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussels
Italy	Istituto Europeo di Oncologia	Milan
Netherlands	Radboud	Nijmegen
United Kingdom	Royal Marsden	London

Sponsors (1)

Lead Sponsor	Collaborator
Byondis B.V.

Countries where clinical trial is conducted

Belgium,  Italy,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities	Part 1	21 days
Secondary	Objective response rate	Part 2	21 days