Etude : BYON5667.002 /



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : BYON5667.002

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 11/01/2022
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Étude multicentrique, randomisée, en double aveugle, contrôlée par placebo avec une période de pré-inclusion à bras unique visant à évaluer la sécurité d'emploi et l’efficacité du collyre de thiosulfate de sodium (BYON5667) pour réduire la toxicité oculaire chez des patients atteints d’un cancer et traités par SYD985

Spécialité : Toutes tumeurs solides
Localisation : C - Toutes localisations

Spécialité : Seins, organes génitaux de la femme
Localisation : C50 - Tumeur maligne du sein
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : 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 ARMS:
- Experimental: BYON5667 & SYD985
BYON5667 eye drops should be self-administered daily during waking hours. SYD985, every 3 weeks (Q3W)

- Placebo Comparator: Placebo & SYD985
Placebo eye drops should be self-administered daily during waking hours. SYD985, every 3 weeks (Q3W)

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 OBJECTIVES:
• 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

Phase : I/II

Stade : Localement avancé à Métastatique

2, 3, 4, X
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 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.

Critères de non-inclusion : 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.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04983238
Promoteur :
Byondis B.V.
Type de sponsor : Industriel
-
00000 HORS FRANCE

Coordonnateur :
clinicaltrials@byondis.com
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Docteur Audrey MAILLIEZ

TEC / ARC / IDE :
Unité Intégrée de Recherche Clinique
investigation@
o-lambret.fr
03.20.29.59.35

Statut de l'essai : OUVERT

MAJ : 11/01/2022