Clinical Trial

A Global, Interventional, Open-label Trial of T-DXd-based Therapy Followed by Palbociclib, Endocrine Therapy and Dual HER2 Blockade in First-line HER2+/HR+ Advanced or Metastatic Breast Cancer and Retreatment with T-DXd (DESTINY Breast Guide)

MOA: Trastuzumab deruxtecan (T-DXd) is a HER2 directed ADC with a topoisomerase I inhibitor payload.

Key Eligibility:

Inclusion Criteria-Upfront Treatment Phase

• Histologically confirmed HR+ and HER2+ la/MBC (local testing)
• No prior chemotherapy or HER2-targeted tx for MBC
  • If treated in (neo)adjuvant setting, pt are eligible if DFI >6 months from
    completion of systemic tx to PD
  • Previous T-DXd tx for eBC with an EFS or DFI of <12 months from
    completion of T-DXd tx in the neoadjuvant or post-neoadjuvant setting
    are excluded
• 1 prior line of ET tx for MBC is allowed
• Prior tx with any CDK inhibitor are excluded
• > 1 measurable lesion or non-measurable bone-only disease or lytic/mixed
  lytic bone lesions assessable by CT, MRI, or X-ray
• Asymptomatic brain metastases (<2 cm) or treated metastases that are no
  long symptomatic and requires no treatment are eligible
• Adequate treatment washout period before enrollment (check full protocol
  for details)

Inclusion Criteria- Maintenance Treatment phase

• No evidence of PD under T-DXd+P per RECIST v1.1 AND
• Pt willing to switch tx AND
• Completed at least 8 cycles of T-DXd+P and achieved cCR OR
• Completed 18 cycles (total) of T-DXd and achieved SD/PR and stable
  disease in last 2 scans) OR has unconfirmed CR
• Pt had no more than 24 cycles of tx with T-DXd+P

Inclusion Criteria- T-DXd Retreatment Phase

• Had received at least 1 dose of Maintenance Treatment
• Has PD per RECIST v1.1 per investigator assessment during Maintenance
  Treatment
• ILD/pneumonitis Grade ≥2 during the Upfront or Maintenance Treatment
  Phases are excluded
• Any unresolved SAE related to prior Maintenance Treatment Phase are
  excluded
• Non-ILD toxicities related to T-DXd in the Upfront Treatment Phase that
  required T-DXd discontinuation are excluded