A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in Participants With High-Risk HER2-Positive Primary Breast Cancer Who Have Residual Invasive Disease in Breast or Axillary Lymph Nodes Following Neoadjuvant Therapy (DESTINY-Breast05)
A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in Participants With High-Risk HER2-Positive Primary Breast Cancer Who Have Residual Invasive Disease in Breast or Axillary Lymph Nodes Following Neoadjuvant Therapy (DESTINY-Breast05)
Patients with HER2-positive primary breast cancer (BC) who do not achieve complete response after appropriate neoadjuvant therapy are at higher risk of disease recurrence. More effective treatment options are needed for this patient population. This study will examine the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) in high-risk patients with residual invasive breast cancer following neoadjuvant therapy.
This study will examine trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive primary BC who have residual invasive disease in breast or axillary lymph nodes with higher risk of recurrence, which includes patients who were inoperable at disease presentation or had pathological node-positive status after neoadjuvant therapy.
The primary objective is to compare invasive disease-free survival (IDFS) between T-DXd and T-DM1 treatment arms in this population. The key secondary objective of the study is to evaluate disease-free survival (DFS).
Key Inclusion Criteria:
Adults ≥18 years old (local regulatory requirements will apply if the legal age of consent for study participation is >18 years old).
Pathologically documented HER2-positive breast cancer (BC):
Histologically confirmed invasive breast carcinoma.
Clinical stage at disease presentation: T1-4, N0-3, M0; patients presenting with T1N0 tumors are not eligible.
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:
Completion of neoadjuvant systemic therapy, including taxane-based chemotherapy and HER2-directed treatment prior to surgery.
Adequate excision as confirmed per medical records: surgical removal of all clinically evident disease in the breast and axillary lymph nodes.
An interval of no more than 12 weeks between the date of last surgery and the date of randomization.
Known hormone receptor (HR) status, per local laboratory assessment, as defined by ASCO-CAP guidelines (≥1%): HR positive 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.
Key Exclusion Criteria:
Stage IV (metastatic) BC.
History of any prior (ipsi- or contralateral) breast cancer except lobular carcinoma in situ (LCIS).
Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery.
Prior treatment with T-DXd, T-DM1 or other anti-HER2 antibody-drug conjugate (ADC) or prior enrollment in a clinical study of T-DXd (regardless of treatment arm)
History of exposure to the following cumulative doses of anthracyclines:
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 with an outcome similar to those mentioned above.
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).
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).
Any autoimmune, connective tissue or inflammatory disorders (eg, Rheumatoid arthritis, Sjogren's, sarcoidosis, etc) where there is documented or a suspicion of pulmonary involvement or pneumonectomy at the time of screening.
Medical history of myocardial infarction (MI) within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), troponin levels consistent with MI as defined according to the manufacturer 28 days prior to randomization.
Lexington, Kentucky 40536, United States
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