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

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

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

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: BYON5667 & SYD985; Drug: Placebo & 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2650
    • University Hospital Antwerp
  • Leuven, Belgium, 3000
    • UZ Leuven
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Paris, France, 75475
    • Hopital Saint Louis
• Spain
  • Barcelona, Spain, 8035
    • Vall d' Hebron
  • L'Hospitalet De Llobregat, Spain, 8908
    • ICO I'Hospitalet - Hospital Duran i Reynals
  • Lleida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain, 28040
    • START Madrid HU Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • START Madrid HU HM Sanchinarro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BYON5667 & SYD985; BYON5667 eye drops should be self-administered daily during waking hours. SYD985, every 3 weeks (Q3W)	Drug: BYON5667 & SYD985; Ocular administration: BYON5667, Intravenous administration: SYD985; Other Names: BYON5667: sodium thiosulfate; SYD985: (vic-)trastuzumab duocarmazine
Placebo Comparator: Placebo & SYD985; Placebo eye drops should be self-administered daily during waking hours. SYD985, every 3 weeks (Q3W)	Drug: Placebo & SYD985; Ocular administration: Placebo, Intravenous administration: SYD985; Other Names: SYD985: (vic-)trastuzumab duocarmazine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocular toxicity	Percentage of patients with SYD985-related ocular toxicity of different grades at Day 63 or Day 126	Day 63 or Day 126
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
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
SYD985-related ocular adverse events (AE)	Time to first SYD985-related ocular AE	Up to 2 years
Discontinuation due to SYD985-related ocular toxicity	Percentage of patients discontinued due to SYD985-related ocular toxicity	Up to 2 years
Efficacy of SYD985 by assessing the objective response rate (ORR)	Efficacy of SYD985	Up to 2 years
Efficacy of SYD985 by assessing the progression-free survival (PFS)	Efficacy of SYD985	Up to 2 years
Efficacy of SYD985 by assessing the overall survival	Efficacy of SYD985	Up to 2 years
Safety of SYD985 by assessing incidence and severity of treatment-emergent drug-related adverse events	Safety of SYD985	Up to 2 years

Collaborators and Investigators

• Sponsor: Byondis B.V.
• Investigators: Study Director: Ellen Mommers, PhD, Byondis B.V., The Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Actual): April 19, 2023
• Study Completion (Actual): June 26, 2023

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): July 30, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Nervous System Diseases; Eye Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Optic Nerve Diseases; Cranial Nerve Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cranial Nerve Injuries; Optic Nerve Injuries; Toxic Optic Neuropathy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Immunological; Anti-Bacterial Agents; Antioxidants; Antidotes; Antitubercular Agents; Chelating Agents; Sequestering Agents; Trastuzumab; Sodium thiosulfate
• Other Study ID Numbers: BYON5667.002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No