Clinical trial NCT05323045: A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate BYON3521
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: ADC
c-MET
solid tumors
Lead sponsor: Byondis B.V.
Sponsor class: INDUSTRY
First posted: 2022-04-12
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose-limiting toxicities
timeFrame: 21 days
Secondary outcomes:
measure: Objective response rate
timeFrame: 21 days
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Nijmegen
country: Netherlands
facility: Radboud
city: London
country: United Kingdom
facility: Royal Marsden
Study officials:
affiliation: Byondis B.V., The Netherlands
name: Tanya Vermaas
role: STUDY_DIRECTOR
References: