Evaluation of Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985

Metastatic Breast Cancer Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial With a Single Arm run-in Period to Evaluate the Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04983238
• Other study ID #: BYON5667.002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 10, 2022
• Est. completion date: June 26, 2023

Study information

• Verified date: January 2024
• Source: Byondis B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 26, 2023
• Est. primary completion date: April 19, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Breast Cancer

Intervention

Drug:
• BYON5667 & SYD985
Ocular administration: BYON5667, Intravenous administration: SYD985
• Placebo & SYD985
Ocular administration: Placebo, Intravenous administration: SYD985

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Antwerp
Belgium	UZ Leuven	Leuven
France	Institut Bergonié	Bordeaux
France	Centre Oscar Lambret	Lille
France	Hôpital Saint Louis	Paris
Spain	Vall d' Hebron	Barcelona
Spain	ICO I'Hospitalet - Hospital Duran i Reynals	L'Hospitalet De Llobregat
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	START Madrid HU Fundacion Jimenez Diaz	Madrid
Spain	START Madrid HU HM Sanchinarro	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Byondis B.V.

Countries where clinical trial is conducted

Belgium,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of BYON5667 eye drops by assessing the percentage of patients with SYD985-related ocular adverse events Grade >=1 at Day 63	Percentage of patients with SYD985-related ocular toxicity Grade =1 at Day 63	63 days
Secondary	Ocular toxicity	Percentage of patients with SYD985-related ocular toxicity of different grades at Day 63 or Day 126	Day 63 or Day 126
Secondary	Tolerability of BYON5667 eye drops by means of Eye Drop Tolerability questionnaire scores	Tolerability of BYON5667 eye drops Questionnaire includes 5 questions with score of 0 (no discomfort) to 10 (most imaginable discomfort)	Up to 2 years
Secondary	National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores	Self-reported validated questionnaire including 25 questions with scores of 1 to maximum 6, from best/worst to worst/best depending on the question	Up to 2 years
Secondary	SYD985-related ocular adverse events (AE)	Time to first SYD985-related ocular AE	Up to 2 years
Secondary	Discontinuation due to SYD985-related ocular toxicity	Percentage of patients discontinued due to SYD985-related ocular toxicity	Up to 2 years
Secondary	Efficacy of SYD985 by assessing the objective response rate (ORR)	Efficacy of SYD985	Up to 2 years
Secondary	Efficacy of SYD985 by assessing the progression-free survival (PFS)	Efficacy of SYD985	Up to 2 years
Secondary	Efficacy of SYD985 by assessing the overall survival	Efficacy of SYD985	Up to 2 years
Secondary	Safety of SYD985 by assessing incidence and severity of treatment-emergent drug-related adverse events	Safety of SYD985	Up to 2 years