DB-07: This phase Ib/II trial aims to explore the safety, tolerability, and anti-tumour activity of a targeted cancer therapy in patients with breast cancer that has not previously been treated using chemotherapy and has spread to other parts of the bodyA Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With HER2-positive Metastatic Breast Cancer (DESTINY-Breast07)

Inclusion

• Patients must be at least 18 years of age

• Pathologically documented breast cancer that:

  1. Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
  2. HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment. The local HER2 result must be from a tumour sample obtained in the metastatic setting.
  3. Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting
• Patient must have adequate tumor sample from the metastatic setting for biomarker assessment
• ECOG Performance Status of 0 or 1

• Part 1

  1. Disease progression on or after the last systemic therapy prior to starting study treatment
  2. At least 1 prior treatment line in metastatic setting required.

• Part 2 (Modules 0 - 5)

  a) No prior lines of therapy for advanced/MBC allowed

• Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed

CNS Inclusion

• Modules 0 - 5 Patients must have no brain metastases or stable brain metastases.
• Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy