A study to evaluate the safety and efficacy of BYON5667 eye drops to reduce ocular toxicity in cancer patients treated with SYD985.

Phase 1

• Conditions: 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: 21.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005575-12-BE
• Lead Sponsor: Byondis B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-31
• Last Update Posted: 18 September 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 205

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
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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified