Titre A Phase 1b Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With Metastatic HER2-low Breast Cancer
Protocole ID DESTINY-Breast08
ClinicalTrials.gov ID NCT04556773
Type(s) de cancer Sein
Phase Phase I
Stade Métastatique
Type étude Clinique
Médicament Trastuzumab Deruxtecan
Institution CHU DE QUEBEC – UNIVERSITE LAVAL
   L'HOTEL-DIEU DE QUEBEC ET CRCEO
      11 Côte du Palais, Québec, QC, G1R 2J6
Ville Québec
Investigateur(trice) principal(e) Dr Vincent Castonguay
Coordonnateur(trice) Maryse Gingras
 418-691-5781
Statut Fermé
Critètes d'éligibilité
  • Patients must be at least 18 years of age
  • Male or female patients who have pathologically documented breast cancer that:
    1. Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay
    2. Is documented as HR+ (either ER and/or PgR positive [ER or PgR ≥1%]) or ER and PgR negative (ER and PgR <1%) per ASCO/CAP guidelines in the metastatic setting
  • Patient must have adequate tumor sample for biomarker assessment
  • ECOG Performance Status of 0 or 1
For patients with HR+ disease:
Part 1: At least 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors), and at least 1 prior line of chemotherapy for MBC are required.
Part 2: Only 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) for MBC is allowed. No prior chemotherapy in the metastatic setting is allowed. Note there are no patients with HR+ disease in Part 2 of Modules 2 and 3.
For patients with HR- disease:
Part 1: At least 1 prior line of chemotherapy for MBC is required. Note there are no patients with HR- disease in Part 1 of Modules 4 and 5.
Part 2: For Module 2, no prior lines of therapy for MBC are allowed, and for Modules 1 and 3, only 1 prior line of chemotherapy for MBC is allowed. Note there are no patients with HR- disease in Part 2 of Modules 4 and 5.
Critètes d'exclusion
  • Uncontrolled intercurrent illness
  • Uncontrolled or siginificant cardiovascular disease
  • History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  • Lung-specific intercurrent clinically significant illnesses
  • Has spinal cord compression or clinically active central nervous system metastases
  • Active primary immunodeficiency
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
  • Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor.