DESTINY-Breast11 will compare trastuzumab deruxtecan (T-DXd) alone or in sequence with other medications, known as THP, with standard of care treatment (ddAC-THP) and determine its safety and efficacy in patients with HER2-positive early breast cancer.
- Conditions
- Early stage HER2-positive breast cancer (T stage >= T3, lymph node positive, or inflammatory)MedDRA version: 21.0Level: LLTClassification code 10025541Term: Malignant breast neoplasmSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-000603-21-ES
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 624
Key Inclusion Criteria:
- Patients must be at least 18 years of age.
- Histologically documented HER2-positive EBC participants with:
(a) Locally assessed HER2-positive (IHC 3+ or ISH+) according to ASCO-CAP guidelines and prospectively centrally confirmed as HER2 positive based on a tumour sample
(b) Unifocal and multifocal tumours (> 1 tumour confined to the same quadrant as the primary tumour) must have 1 focus sampled and centrally confirmed as HER2 positive
(c) Multi-centric tumours (multiple tumours involving > 1 quadrant of the breast) must have 1 lesion from each involved quadrant sampled and centrally confirmed as HER2 positive. All quadrants tested must be centrally confirmed as HER2 positive
(d) Tumours documented as HR-positive (either ER and/or PgR positive [ER or PgR = 1%]) or HR-negative (ER and PgR negative) by local assessment per ASCO-CAP guidelines (Allison et al 2020)
(e) Clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or = T3, N0, M0 as determined by the AJCC staging system, 8th edition (Hortobagyi et al 2017)
(f) Pathologic confirmation of nodal involvement with malignancy as determined by fine-needle aspiration or core-needle biopsy, when applicable.
- FFPE tissue block (2 cores) or 20 freshly-cut, serial tumor slides for HER2 assessment by central lab. If blocks are incomplete or fewer than 20 slides are available, participants may be eligible following discussion with the AstraZeneca Study Physician?
- ECOG performance status of 0 or 1 at randomization
- Adequate organ and bone marrow function
- LVEF = 50% within 28 days before randomization
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 530
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 94
Key Exclusion Criteria:
- Prior history of invasive breast cancer
- Any primary malignancy within 3 years, except adequately resected non-melanoma skin cancer, or curatively treated in situ disease
- History of DCIS, except for participants treated with mastectomy only > 5 years prior to current diagnosis
- Prior sentinel lymph node biopsy or axillary lymph node dissection before initiation of neoadjuvant treatment
- Prior systemic therapy for the treatment of breast cancer
- Previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy; cyclophosphamide allowed for non-cancer treatment if last dose > 6 months
- Ineligible for any medication in the control Arm C
- Any concurrent anticancer treatment
- History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any pulmonary disorder
- Investigator judgement of 1 or more of the following:?
(a) Mean resting corrected QTcF interval of >470 ms (females) or >450 ms (males)?
(b) History of QT prolongation associated with other medications that required discontinuation of that medication or any medication known to prolong QT interval and cause TdP.?
(c) Congenital long QT syndrome, family history of long QT syndrome or unexplained death under 40 years in first degree relatives
- History of arrhythmia, symptomatic or uncontrolled atrial fibrillation or asymptomatic sustained ventricular tachycardia
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method