A first-in-human dose-escalation and expansion study 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.

Recruiting

Conditions: cancer
carcinoma
10027476

Registration Number: NL-OMON56017

Lead Sponsor: Fortrea Belgium SR

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 36

Inclusion Criteria

D4a Inclusion criteria
In English
1. Male or female, age >=18 years at the time of signing first informed consent;
2. 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-squmous non small cell lung cancer (non-squamous NSCLC) (see
exclusion 1.f);;
• Cohort B: Specific gynaecological cancers: ovarian cancer, endometrial cancer,
cervical cancer;
• Cohort C: HNSCCPancreatic
adenocarcinoma (PA););
• Cohort D: Uveal melanoma
(UM).;

3. Part 1: Tumour c-MET positive membrane staining by immunohistochemistry
(IHC)a and/or MET amplification by dual In Situ Hybridization (dISH)a and/or
known MET-mutation (excluding exon14m)b on most recent available/obtained
tumour material from a site not previously irradiated;
a as determined by the central laboratory, b in agreement with sponsor
art 2: Tumour c-MET membrane expression by immunohistochemistry (IHCor tumour
c-MET positive membrane staining by immunohistochemistry (IHC) and MET-mutation
(excluding exon14m) score >= 2+) as determined by the central laboratory on
most recent available/obtained tumour material from a site not previously
irradiated;
4. Presence of a tumour lesion accessible for biopsy and patient should be
willing to undergo a fresh tumour biopsy, unless adequate biopsy material is
available obtained not more than 6 months prior to signing main informed
consent;
5. Eastern Cooperative Oncology Group (ECOG) performance status <= 1;
6. Adequate organ function, evidenced by the following laboratory results:
- Absolute neutrophil count >= 1.5 x 109/L;
- Platelet count >= 100 x 109/L;
- Hemoglobin >= 9.0 g/dL or 5.6 mmol/L;
- Total bilirubin <= 1.5 x the upper limit of normal (ULN);
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3.0 x
ULN (or <= 5.0 x ULN in the presence of liver metastases);
- Serum creatinine <= 1.5 x ULN;
- Estimated Glomerular Filtration Rate (eGFR)* >= 60 ml/min/1.73 m2;
*preferably calculated with CKD-EPI formula
7. Highly effective contraception must be used during the trial and up to at
least 8 months after last IMP treatment for women of childbearing potential and
up to at least 6 months after last IMP treatment for male patients with a
female partner of childbearing potential. This is not required in case the
patient or sole partner is surgically sterilized or in case the patient truly
abstains from sexual activity;

Additional inclusion criteria for Part 2 only
8. At least one measurable cancer lesion as defined by the Response Evaluation
Criteria for Solid Tumours (RECIST version 1.1);

D4a Main inclusion crititeria
In Dutch
1Man of vrouw, leeftijd >= 18 jaar op het moment van ondertekening van de eerste
geïnformeerde toestemming;
2Patiënt met histologisch bevestigde, lokaal gevorderde of gemetastaseerde
kanker die progressie heeft vertoond met standaardbehandeling of voor wie geen
standaardbehandeling bestaat:
*Deel 1 (dosisescalatie): solide tumoren van elke oorsprong;
*Deel 2 (uitbreiding): • Cohort A: Niet-squameuze, niet-kleincellige longkanker
(niet-squameus NSCLC) (zie uitsluiting 1.f);
• Cohort B: Specifieke

Exclusion Criteria

D5. Exclusion criteria
In English
1. Having been treated with:
a. DUBA-containing antibody-drug conjugates (ADCs) at any time;
b. c-MET targeting cytotoxic agents at any time, including ADC with cytotoxic
payload;
c. Other anticancer therapy including chemotherapy, immunotherapy, c-MET
targeting agent or investigational agent within 4 weeks prior to start IMP
treatment or within 5 times the elimination half-life of the therapy, whatever
is shorter;
d. Radiotherapy within 4 weeks prior to start IMP treatment, or within 1 week
for palliative care (as long as the lungs were not exposed);
e. Hormone therapy (except for gonadotropin-releasing hormone (GnRH) agonists
for prostate cancer or premenopausal breast cancer) within 1 week prior to
start IMP treatment;
f. Cohort A (non-squamous NSCLC) only: EGFR inhibitors or eligible for EGFR
inhibitors at any time;
The patient must have sufficiently recovered from any treatment-related
toxicities to CTCAE Grade <=1 or baseline, except for toxicities not considered
a safety risk for the patient at the investigator*s discretion; (e.g. alopecia
or skin hyperpigmentation);
2. History of hypersensitivity or allergic reaction to any of the excipients of
the IMP treatment which led to permanent discontinuation of the treatment;
3. Known presence of a tumour harboring MET exon14 mutation; (Part 1 only);
4. History or presence of keratitis;
5. History or presence of glomerulonephritis, acute tubular necrosis and/or
interstitial nephritis, or clinically significant findings as determined by
urinalysis at screening (see Section 9.12, Figure 1);
6. History or presence of idiopathic pulmonary fibrosis, organizing pneumonia
(e.g. bronchiolitis obliterans), drug-induced or idiopathic pneumonitis, or
evidence of active pneumonitis on screening chest CT scan;
7. 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;
8. Severe, uncontrolled systemic disease (e.g. clinically significant renal,
cardiovascular, pulmonary, metabolic disease, skin disease, or autoimmune
disease including
Sjogren*s syndrom)) at screening;
9. Symptomatic brain metastases, brain metastases requiring steroids to manage
symptoms, or treatment for brain metastases within 8 weeks prior to start IMP
treatment;
10. Known active Hepatitis B, C or E infection at screening; (prior infections
are not
excluded);
11. Major surgery within 4 weeks prior to start IMP treatment;
12. Pregnancy or lactation;
13. Other condition that in the investigator*s opinion is likely to jeopardize
patient safety or interfere with the patient*s ability to comply with study
requirements.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint for Part 1 of the trial is:<br /><br>• Incidence of DLTs.<br /><br><br /><br>The primary endpoint for Part 2 of the trial is:<br /><br>• ORR (Cohort A-D).<br /><br><br /><br>ORR is defined as the percentage of patients with a best overall tumour<br /><br>response of complete response (CR) or partial response (PR) according to RECIST<br /><br>1</p><br>

Secondary Outcome Measures