Etude de phase 3, randomisée, évaluant le trastuzumab déruxtécan, chez des patients ayant un adénocarcinome de l’estomac ou de la jonction gastro-oesophagienne (JGO) métastatique et/ou non résécable, HER2 positif et ayant progressé pendant ou après un schéma thérapeutique contenant du trastuzumab

Essai clinique

Type : Industriel
Statut : Ouvert
Phase : III
Étape du traitement : Thérapie ciblée
Date d'ouverture : 21/05/2021
Date clôture : 15/11/2024
Promoteur : Daiichi Sankyo, Inc.
Progression du cancer: À distance
Résumé :

This study will assess the efficacy and safety of T-DXd compared with Ram + PTX in participants with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) gastric or GEJ adenocarcinoma (based on [American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines and confirmed by central assessment of tumor tissue) who have progressed on or after a trastuzumab-containing regimen and have not received any additional systemic therapy. Participants will be randomized 1:1 to either T-DXd or Ram + PTX treatment. The primary objective will assess overall survival. Secondary objectives will further assess progression-free survival, objective response rate, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity of T-DXd.

Domaines/spécialités :
  • Cancers digestifs
    • Œsophage
    • Estomac
Biomarqueurs :
  • HER2
Pathologies :
  • Tumeur maligne de l'estomac - Cim10 : C16
  • Carcinome in situ de la cavité buccale, de l'oesophage et de l'estomac - Cim10 : D00
Liens externes :

Critères de population

Sexe : Homme et femme
Age minimum : 18 ans
Critères d’inclusion :
  • Adults (according to local regulation) and able to provide informed consent for study participation.
  • Pathologically documented gastric and GEJ adenocarcinoma that has been previously treated in the metastatic setting (unresectable, locally advanced, or metastatic disease).
  • Progression on or after first-line therapy with a trastuzumab or approved trastuzumab biosimilar-containing regimen. Note: Prior neoadjuvant or adjuvant therapy with a trastuzumab-containing regimen can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy. Prior neoadjuvant or adjuvant therapy that does not include trastuzumab will not be counted as a line of therapy regardless of the progression status of the subject.
  • Centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy obtained after progression on or after a first-line trastuzumab or approved trastuzumab biosimilar-containing regimen.
  • Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening.
  • Adequate bone marrow, renal, and hepatic function within 14 days of randomization.
Critères d’exclusion :
  • Use of anticancer therapy after trastuzumab-containing treatment
  • Medical history of myocardial infarction (MI) within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV).
  • Has a QT interval corrected by Fridericia's formula (QTcF) prolongation to >470 msec (female subjects) or >450 msec (male subjects) based on average of the Screening triplicate12-lead ECG.
  • Has a history of (non-infectious) interstitial lung disease (ILD/pneumonitis) that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
  • Any autoimmune, connective tissue or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented (or a suspicion of) pulmonary involvement at the time of Screening.
  • Prior complete pneumonectomy.
  • Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
  • Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated.
  • History of severe hypersensitivity reactions to either the T-DXd or inactive ingredients in T-DXd.
  • History of severe hypersensitivity reactions to other monoclonal antibodies, including ramucirumab or to any of its excipients.
  • Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.
  • Current uncontrolled infection requiring antibiotics, antivirals, or antifungals or an unexplained fever >38.0°C during Screening visits or on the first scheduled day of dosing (at the discretion of the Investigator, participants with tumor fever may be enrolled), which in the Investigator's opinion might compromise the participant's participation in the study or affect the study outcome
  • Clinically significant gastrointestinal disorder (eg, including hepatic disorders, bleeding, inflammation, occlusion, ileus, diarrhea Grade >1, jaundice, intestinal paralysis, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction) in the opinion of Investigator

Centre d'investigation

En cours
Nom : CHRU de Besançon
Ville : BESANÇON (25)
RESPONSABLE MÉDICAL
Aucun responsable médical renseigné
CONTACT TECHNIQUE
Nom : BERTHOD
Prénom : Diane
Téléphone : 03 70 63 24 03
Email : dberthod@chu-besancon.fr

Référentiels Oncologik

  • Estomac
  • Adénocarcinome de l'œsophage et de la jonction œsogastrique