DESTINY-Breast03 trial summary

Overview

• Title: DS-8201a (trastuzumab deruxtecan) versus T-DM1 for HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane (DESTINY-Breast03).
• ClinicalTrials.gov ID: NCT03529110.
• Sponsor: Daiichi Sankyo; collaborators include AstraZeneca.
• Phase: Phase 3, randomized, open-label, active-controlled, parallel assignment.
• Primary purpose: Treatment.
• Enrollment: 524 participants (actual).
• Study status: Active, not recruiting.
• Study start: 2018-08-09 (actual); primary completion: 2021-05-21 (actual); estimated study completion: 2026-07-30.
• Results first posted: 2022-04-29; last update posted: 2025-10-21.

Interventions and Arms

• Experimental arm: Trastuzumab deruxtecan (T-DXd; DS-8201a), IV 5.4 mg/kg every 3 weeks (Q3W).
• Active comparator arm: Ado-trastuzumab emtansine (T-DM1), administered per approved label.
• Both arms enrolled participants previously treated with trastuzumab and a taxane.

Key Inclusion/Exclusion Criteria

• Inclusion:
  • Adults ≥18 years able to provide informed consent.
  • Pathologically documented unresectable or metastatic breast cancer.
  • HER2-positive status confirmed centrally per ASCO-CAP guidelines.
  • Prior trastuzumab and taxane in advanced/metastatic setting or progression within 6 months after neoadjuvant/adjuvant trastuzumab-taxane.
  • Radiologic progression during/after most recent treatment or within 6 months after adjuvant therapy.
  • At least one measurable lesion per mRECIST v1.1; central HER2 confirmation from most recent tissue or fresh biopsy.
• Exclusion:
  • Prior anti-HER2 ADC (e.g., T-DM1) in metastatic setting (adjuvant/neoadjuvant T-DM1 allowed if no progression within 12 months).
  • Uncontrolled/significant cardiovascular disease (recent MI, symptomatic CHF NYHA II–IV, QTc prolongation, LVEF <50%).
  • History of noninfectious ILD/pneumonitis requiring steroids, current ILD/pneumonitis, or suspected ILD not ruled out by imaging.
  • Untreated or symptomatic CNS metastases or spinal cord compression; treated inactive brain metastases may be eligible after recovery.
  • Severe hypersensitivity to study drugs or other monoclonal antibodies.

Outcomes Measured

• Primary Outcome:
  • Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR); time from enrollment to documented progression or death. Time frame: up to 33 months (data cut-off).
• Key Secondary Outcomes:
  • Overall Survival (OS): time from first dose to death. Time frame: up to 33 months.
  • Objective Response Rate (ORR) by BICR and investigator: confirmed CR or PR per RECIST v1.1. Time frame: up to 33 months.
  • Duration of Response (DoR) by BICR and investigator: time from first documented CR/PR to progression or death. Time frame: up to 33 months.
  • PFS by investigator assessment. Time frame: up to 33 months.

Study Design Details

• Allocation: Randomized.
• Model: Parallel assignment with two arms (T-DXd vs T-DM1).
• Masking: Open-label (no masking).
• Primary endpoint assessed by BICR; investigator assessments used for secondary analyses.
• IPD sharing: De-identified individual participant data and supporting documents available on request via Vivli (access criteria and timelines specified).

Locations

• Multinational trial with 164 locations across multiple countries, including major sites in:
  • United States (multiple academic cancer centers).
  • Japan, China, South Korea.
  • Europe (France, Germany, Belgium, Italy, Spain, United Kingdom).
  • Australia, Brazil, Canada, Taiwan, Hong Kong.
• Examples of participating centers: Dana-Farber (Boston), MD Anderson (Houston), National Cancer Center (Tokyo), Institut Gustave Roussy (Villejuif), Peter MacCallum Cancer Centre (Melbourne).

Documents and Publications

• Study protocol and statistical analysis plan available (Prot_SAP_001.pdf).
• Key publications (selected):
  • NEJM primary report (Cortes J. et al., 2022).
  • Lancet updated results (Hurvitz SA. et al., 2023).
  • Nature Medicine long-term survival analysis (Cortes J. et al., 2024).
  • Multiple additional analyses and meta-analyses on efficacy, safety, and patient-reported outcomes.

Decisions

• Sponsor: Daiichi Sankyo responsible party; collaborators include AstraZeneca.
• Plan for data sharing: IPD available to qualified researchers under specified criteria via Vivli.

Action Items

• For data access: submit formal request to Vivli per Daiichi Sankyo access criteria.
• For site-specific inquiries: contact listed study locations or responsible party (Daiichi Sankyo) via ClinicalTrials.gov contacts.