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

Byondis

Status and phase: Completed; Phase 1

Conditions: Solid Tumor

Treatments: Drug: BYON3521

Study type: Interventional

Funder types: Industry

Identifiers

NCT05323045

BYON3521.001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

---

31 participants in 1 patient group

BYON3521

Experimental group

Description:

c-MET targeting Antibody-Drug Conjugate

Treatment:

Drug: BYON3521