Metastatic Breast Cancer
Conditions
Brief summary
This multicenter, randomized, double-blind, placebo-controlled trial with a single arm run-in period is to evaluate the safety and efficacy of sodium thiosulfate (BYON5667) eye drops to reduce ocular toxicity in cancer patients treated with the antibody-drug conjugate (ADC) SYD985
Detailed description
This multicenter trial has a single arm run-in period followed by a randomized, placebo-controlled, double-blind comparative part. In the single arm part of the trial, patients with HER2-expressing locally advanced or metastatic solid tumours will be enrolled and treated with the antibody-drug conjugate (ADC) SYD985 once every 3 weeks until disease progression or unacceptable toxicity. All patients will receive concomitant BYON5667 eye drops. When the primary safety and efficacy analysis of the BYON5667 eye drops at Day 63 is favorable, the trial may continue to the comparative part in which patients with locally advanced or metastatic HER2-positive breast cancer will be treated with SYD985. Patients will be randomly assigned (1:1) to receive BYON5667 or placebo eye drops.
Interventions
DRUGBYON5667 & SYD985
Ocular administration: BYON5667, Intravenous administration: SYD985
DRUGPlacebo & SYD985
Ocular administration: Placebo, Intravenous administration: SYD985
Sponsors
Byondis B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main 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 human epidermal growth factor receptor 2 (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 refrain from wearing any kind of contact lenses during trial treatment; 6. Adequate organ function Main
Exclusion criteria
1. Current or previous use of prohibited medication as listed in the protocol 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%, 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 or presence of clinically significant cardiovascular disease; 7. Severe, uncontrolled systemic disease; 8. Symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of BYON5667 eye drops by assessing the percentage of patients with SYD985-related ocular adverse events Grade >=1 at Day 63 | 63 days | Percentage of patients with SYD985-related ocular toxicity Grade ≥1 at Day 63 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of BYON5667 eye drops by means of Eye Drop Tolerability questionnaire scores | Up to 2 years | Tolerability of BYON5667 eye drops Questionnaire includes 5 questions with score of 0 (no discomfort) to 10 (most imaginable discomfort) |
| National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores | Up to 2 years | Self-reported validated questionnaire including 25 questions with scores of 1 to maximum 6, from best/worst to worst/best depending on the question |
| SYD985-related ocular adverse events (AE) | Up to 2 years | Time to first SYD985-related ocular AE |
| Discontinuation due to SYD985-related ocular toxicity | Up to 2 years | Percentage of patients discontinued due to SYD985-related ocular toxicity |
| Ocular toxicity | Day 63 or Day 126 | Percentage of patients with SYD985-related ocular toxicity of different grades at Day 63 or Day 126 |
| Efficacy of SYD985 by assessing the progression-free survival (PFS) | Up to 2 years | Efficacy of SYD985 |
| Efficacy of SYD985 by assessing the overall survival | Up to 2 years | Efficacy of SYD985 |
| Safety of SYD985 by assessing incidence and severity of treatment-emergent drug-related adverse events | Up to 2 years | Safety of SYD985 |
| Efficacy of SYD985 by assessing the objective response rate (ORR) | Up to 2 years | Efficacy of SYD985 |
Countries
Belgium, France, Spain
Outcome results
None listed