cancer carcinoma
Conditions
Interventions
Dose escalation schedule
To determine the MTD of BYON3521, an adaptive approach using a Continual
Reassessment Method (N-CRM) model will be used. The standard dose selection in
a N-CRM model is base
• Dose strengths above 3.2 up to 4.8 mg/kg: 50%
• Dose strengths above 4.8 mg/kg: 33%.
Sponsors
Fortrea Belgium SRL
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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 = 1.5 x 109/L; - Platelet count >= 100 x 109/L; - Hemoglobin >= 9.0 g/dL or 5.6 mmol/L; - Total bilirubin = 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint for Part 1 of the trial is: • Incidence of DLTs. The primary endpoint for Part 2 of the trial is: • ORR (Cohort A-D). ORR is defined as the percentage of patients with a best overall tumour response of complete response (CR) or partial response (PR) according to RECIST 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| 12.2.2. Secondary endpoints 12.2.2.1. Safety endpoints The endpoints related to safety include: • Incidence and severity of (serious) AEs; • Changes in vital signs and weight; • Changes in ECOG performance status; • Changes in laboratory parameters; • Percentage of patients with confirmed anti-BYON3521 antibodies; • Number of patients with dose modifications due to AEs. 12.2.2.2. Efficacy endpoints Preliminary efficacy will be assessed by: • ORR (Part 1); • Clinical benefit rate (CBR); • Best overall response (BOR); • Best percent change in target lesion measurements; • Time to response; • Duration of response (DOR); • Progression-free survival (PFS); • Overall survival (OS) (Part 2). CBR is defined as the percentage of patients with CR, PR, SD or non-CR/non-PD (SD or non-CR/non-PD for 6 or more months). BOR is defined as the number of patients with CR, PR, stable disease (SD) and progressive disease (PD), patients must have a valid tumour assessment of SD at least 35 days after their first dose of study treatment for this to be considered as their best response; Time to response is defined as the time from first day of IMP treatment to first observation of CR or PR. DOR is defined as the duration from first observation of response (CR or PR) to the time of disease progression or death from any cause. PFS is defined as the time from first day of IMP treatment to disease progression or death from any cause. OS is defined as the time from first day of IMP treatment to death from any cause. 12.2.2.3. Pharmacokinetic endpoints PK endpoints will include standard parameters such as Cmax, tmax, area under the curve (AUC), Cmin (trough-levels), terminal half-life (t*), volume of distribution, and drug clearance. 12.2.2.4. Other endpoints Genetic tumour analysis and SLFN11 analysis will be summarized and correlated, if feasible, with response data. | — |
Countries
Netherlands
Outcome results
None listed