Single arm run-in period: Patients with solid tumours (excluding gastric tumours and adenocarcinomas of the gastroesophageal junction) Randomized part of the study: patients with locally advanced or metastatic HER2-positive breast cancer MedDRA version: 21.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.1 Level: PT Classification code 10055113 Term: Breast cancer
Conditions
Sponsors
Byondis B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, age =18 years at the time of signing first informed consent; 2. Patient with histologically-confirmed, unresectable locally advanced or metastatic cancer with the following restriction: Single arm part: patient with solid tumours of any origin (excluding gastric tumours and adenocarcinomas of the gastroesophageal junction) who has progressed on standard therapy or for whom no standard therapy exists; Randomized part: patient with breast cancer who had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease, or progression during or after [ado-]trastuzumab emtansine treatment for locally advanced or metastatic disease; 3. HER2 tumour status as determined by a local laboratory using immunohistochemistry (IHC) and/or in situ hybridization (ISH): Single arm part: at least IHC 1+; Randomized part: IHC 3+ and/or ISH positive; 4. Eastern Cooperative Oncology Group (ECOG) performance status = 1; 5. Patient should be able to self-administer eye drops up to 6-times daily or should have adequate daily assistance available (e.g. caregiver) to administer the eye drops; 6. Patient should refrain from wearing any kind of contact lenses during trial treatment; 7. 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; 8. For women of childbearing potential and male patients with a female partner of childbearing potential, highly effective contraception must be used during the trial and up to at least 6 months after last IMP treatment. This is not required in case the patient or sole partner is surgically sterilized or in case the patient truly abstains from sexual activity. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 164 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 41
Exclusion criteria
Exclusion criteria: Exclusion criteria 1. Having been treated with: a. DUBA-containing antibody-drug conjugates (ADCs) at any time; b. Anthracycline treatment within 8 weeks prior to start SYD985 treatment; c. Other anticancer therapy including chemotherapy, immunotherapy, or investigational agent within 4 weeks prior to start SYD985 treatment or within 5 times the half-life of the therapy, whatever is shorter; d. Radiotherapy within 4 weeks prior to start SYD985 treatment, or within 1 week for palliative care (as long as the lungs were not exposed); e. Hormone therapy (except for luteinizing hormone-releasing hormone agonists for prostate cancer or premenopausal breast cancer) within 1 week prior to start SYD985 treatment; 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; 2. History of infusion-related reactions and/or hypersensitivity to trastuzumab containing treatment or excipients of the trial treatments which led to permanent discontinuation of the treatment; 3. History or presence of keratitis; 4. Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous trastuzumab containing treatment leading to permanent discontinuation of treatment; 5. 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; 6. History (within 6 months prior to start SYD985) or presence of clinically significant cardiovascular disease such as unstable angina, congestive heart failure, myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication; 7. Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening; 8. Symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to start SYD985 treatment; 9. Positive COVID-19 test within 8 weeks prior to start SYD985 treatment, presence of clinically significant symptoms of confirmed or unconfirmed suspected COVID-19 infection at screening (regardless if and when patient was tested), presence of COVID-19 related signs on screening chest CT scan, or need for continued supportive medication for past COVID-19 infection; 10. Known active Hepatitis B, C or E infection at screening; 11. Major surgery within 4 weeks prior to start SYD985 treatment; 12. Pregnancy or lactation; 13. Other condition, which in the opinion of the investigator, would compromise the safety of the patient or the patient’s ability to complete the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Safety and tolerability of BYON5667 eye drops administered up to 6-times daily by assessing incidence and severity of BYON5667-related AEs; • Efficacy of BYON5667 eye drops by assessing the percentage of patients with SYD985-related ocular toxicity Grade =1 at Day 63. ;Secondary Objective: • Tolerability of BYON5667 eye drops by means of Eye Drop Tolerability questionnaire scores; • National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) scores; • Percentage of patients with SYD985-related ocular toxicity Grade =2 and Grade =3 at Day 63; • Percentage of patients with SYD985-related ocular toxicity Grade =1, Grade =2, and Grade =3 at Day 126; • Time to first SYD985-related ocular AE of Grade =1, Grade =2, and Grade =3; • Percentage of patients who discontinued SYD985 treatment due to SYD985-related ocular toxicity; • Efficacy of SYD985 by assessing the objective response rate (ORR), progression-free survival (PFS), and overall survival; • Safety of SYD985 ;Primary end point(s): The primary safety endpoint of this trial is: • Incidence and severity of BYON5667-related AEs. The primary efficacy endpoint of this trial is: • Percentage of patients with SYD985-related ocular toxicity Grade =1 at Day 63. ;Timepoint(s) of evaluation of this end point: Study assessments and procedures will be performed as outlined in the Protocol (Trial Flow Chart). The first primary efficacy analysis will be performed when 20 patients completed the Day 63 assessments (i.e. Cycle 4 Day 1 visit), or discontinued due to SYD985-related ocular toxicity prior to this visit. It is anticipated that an overall analysis for the single arm part of the trial will be performed when all patients completed the Day 126, i.e. after completion of approximately 4 months of treatment, or have discontinued prematurely. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary safety endpoints of this trial are: • Incidence and severity of (serious) AEs; • Eye Drop Tolerability questionnaire scores; • National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores; • Percentage of patients who discontinued SYD985 treatment due to SYD985-related ocular toxicity; • Changes in vital signs and weight; • Changes in ophthalmological examination and laboratory parameters; • Number of patients with SYD985 dose modifications due to AEs. The secondary efficacy endpoints of this trial are: • Percentage of patients with SYD985-related ocular toxicity Grade =2 and Grade =3 at Day 63; • Percentage of patients with SYD985-related ocular toxicity Grade =1, Grade =2, and Grade =3 at Day 126; • Time to first SYD985-related ocular AE of Grade =1, Grade =2, and Grade =3; • Objective response rate (ORR); • Progression-free survival (PFS); • Overall survival. ;Timepoint(s) of evaluation of this end point: Study assessments and procedures will be performed as outlined in the Protocol (Trial Flow Chart). | — |
Countries
Belgium, France
Contacts
Public ContactClinical Project Leader
Byondis B.V.
Outcome results
None listed