A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in Subjects with High-Risk HER2-Positive Primary Breast Cancer Who Have Residual Invasive Disease in Breast or Axillary Lymph Nodes Following Neoadjuvant Therapy. (DESTINY-Breast05)
- Conditions
- C50 Cancer de mama
- Registration Number
- PER-004-21
- Lead Sponsor
- DAIICHI SANKYO, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- In enrollment
- Sex
- All
- Target Recruitment
- 96
* Has adequate organ function within 14 days before randomization.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.
* Left ventricular ejection fraction (LVEF) =50% within 28 days prior to randomization.
* Known HR status, per local laboratory assessment, as defined by ASCO-CAP guidelines (=1%): HRpositive status defined by either positive estrogen receptor (ER) and/or positive progesterone receptor (PR) status. HR-negative status defined by both known negative ER and known negative PR.
* An interval of no more than 12 weeks between the date of last surgery and the date of randomization.
* Adequate excision as confirmed per medical records: surgical removal of all clinically evident disease in the breast and lymph nodes.
* Completion of neoadjuvant systemic chemotherapy, including taxane and HER2-directed treatment prior to surgery.
Systemic therapy must consist of at least 6 cycles of chemotherapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab (± pertuzumab) and at least 9 weeks of taxane based chemotherapy. Patients may have received an anthracycline as part of neoadjuvant therapy in addition to taxane chemotherapy.
* Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes following completion of neoadjuvant therapy meeting one of the following high-risk criteria.
- Inoperable breast cancer at presentation (prior to neoadjuvant therapy), defined as clinical stages T4, N0-3, M0 or T1-3, N2-3, M0.
- Operable at presentation, defined as clinical stages T1-3,N0-1,M0, with axillary node positive disease (ypN1-3) following neoadjuvant therapy.
* Clinical stage at disease presentation: T1-4, N0-3, M0 (Note: Patients presenting with T1N0 tumors will not be eligible).
* Histologically confirmed invasive breast carcinoma.
* Pathologically documented HER2-positive BC:
- HER2-positive expression defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) (as defined in 2018 American Society of Clinical Oncology – College of American Pathologists [ASCO-CAP] guidelines29), confirmed by a
•Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to randomization
•Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior lobectomy or pneumonectomy.
•Known pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within three months prior to randomization, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease).
•History of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids and/or has ILD/pneumonitis noted on computed tomography (CT) scan of the chest at Screening (asymptomatic interstitial changes confined to recent radiation therapy fields are not excluded).
•History of other malignancy within the last 5 years except for appropriately treated CIS of the cervix, nonmelanoma skin carcinoma, Stage I melanoma skin carcinoma, Stage I uterine cancer, or other appropriately treated non-breast malignancies
•History of exposure to the following cumulative doses of anthracyclines:
- Doxorubicin > 240 mg/m2
- Epirubicin or Liposomal Doxorubicin-Hydrochloride > 480 mg/m2
- For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2
•Prior treatment with T-DXd, T-DM1 or other anti-HER2 antibody-drug conjugate (ADC)
•Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery.
•History of any prior (ipsi- or contralateral) breast cancer except lobular carcinoma in situ (LCIS).
•Stage IV (metastatic) BC.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method IDFS will be determined based on<br>disease recurrence per Investigator assessment based on all available clinical assessments.<br> NAME OF THE RESULT: Invasive disease-free survival (IDFS)<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: After at least 145<br>IDFS events are recorded for interim analysis and 207 IDFS events are recorded for final<br>analysis.
- Secondary Outcome Measures
Name Time Method