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

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: BYON3521

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tanya Vermaas; Phone Number: +31 (0)24 679 5100; Email: clinicaltrials@byondis.com

Study Locations

• Belgium
  • Brussels, Belgium
    • Recruiting
    • Institut Jules Bordet
    • Contact: Nuria Kotecki
• Italy
  • Milan, Italy, 1070
    • Recruiting
    • Istituto Europeo Di Oncologia
    • Contact: Curigliano Giuseppe
• Netherlands
  • Nijmegen, Netherlands, 6500HB
    • Recruiting
    • Radboud
    • Contact: Carla van Herpen
• United Kingdom
  • London, United Kingdom, SM2 5PT
    • Recruiting
    • Royal Marsden
    • Contact: Udai Banerji

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Byondis B.V.
• Investigators: Study Director: Tanya Vermaas, Byondis B.V., The Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: April 4, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): May 26, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: solid tumors; ADC; c-MET
• Other Study ID Numbers: BYON3521.001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No