Clinical trial comparing Trastuzumab Deruxtecan with Trastuzumab Emtansine in high-risk HER2-positive patients with residual breast cancer following neoadjuvant therapy
- Conditions
- High-Risk HER2-Positive Breast CancerMedDRA version: 23.0Level: PTClassification code 10065430Term: HER2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-003982-20-FR
- Lead Sponsor
- Daiichi Sankyo Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1600
1. Sign and date the tissue screening and main ICFs, prior to the start of any study-specific qualification procedures.
2. Adults =18 y old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old).
3. HER2-positive breast cancer, meeting all of the criteria listed in the protocol (see protocol for full details).
4. Histologically confirmed invasive breast carcinoma at time of disease presentation. Subjects with inflammatory breast cancer are allowed providing all eligibility criteria are met.
5. Clinical stage at disease presentation of T1-4, N0-3, M0 prior to neoadjuvant therapy (Note: Patients presenting with T1N0 tumors will not be eligible).
6. Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes following completion of neoadjuvant therapy meeting one of the high risk criteria described in detail in the protocol.
7. Completion of neoadjuvant systemic chemotherapy and HER2-directed treatment.
8. Adequate excision as confirmed per medical records: surgical removal of all clinically evident disease in the breast and lymph nodes (see Section 8.1.2).
9. An interval of no more than 12 weeks between the date of last surgery and the date of randomization.
10. 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) or positive progesterone receptor (PR) status. HR-negative status defined by both known negative ER and known negative PR.
11. Left ventricular ejection fraction (LVEF) = 50% within 28 days prior to randomization.
12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
13. Has adequate organ function within 14 days before randomization as defined in the protocol.
14. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 4 months for males and 7 months for females after the last dose of study drug. See protocol for full details
15. Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study.
16. Female subjects must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.
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 1464
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 136
1. Stage IV (metastatic) breast cancer.
2. History of any prior (ipsi- or contralateral) breast cancer except lobular carcinoma in situ (LCIS).
3. Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery (see Section 8.1.2.1).
4. An overall response of progressive disease according to the investigator at the conclusion of preoperative systemic therapy
5. Prior treatment with T-DXd, T-DM1 or other anti-HER2 ADC.
6. History of exposure to the following cumulative doses of anthracyclines (see protocol for full details).
7. History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ (CIS) of the cervix, non-melanoma skin carcinoma, Stage I melanoma skin carcinoma, Stage I uterine cancer, or other appropriately treated non-breast malignancies.
8. History of (noninfectious) ILD/pneumonitis that required steroids 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).
9. 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, etc.).
10. Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior lobectomy or pneumonectomy.
11. Uncontrolled or significant cardiovascular disease, including: 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.
12. Has a corrected QT interval per Fridericia’s formula (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on screening 12-lead electrocardiogram (ECG).
13. History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
14. History of severe hypersensitivity reactions to other monoclonal antibodies (MAb).
15. Inadequate washout period before Randomization/Cycle 1 Day 1, as defined in the protocol.
16. Substance abuse or medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results.
17. Social, familial, or geographical factors that would interfere with study participation or follow-up.
18. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
19. Known human immunodeficiency virus (HIV) infection or active hepatitis B or C infection.
20. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade = 1 or baseline.
21. Is pregnant or breastfeeding or planning to become pregnant.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate IDFS with T-DXd treatment as compared to T-DM1 ;Secondary Objective: - To evaluate DFS with T-DXd treatment as compared to T-DM1<br>- To evaluate OS with T-DXd treatment as compared to T-DM1<br>- To evaluate DRFI with T-DXd treatment as compared to T-DM1<br>- To evaluate BMFI with T-DXd treatment as compared to T-DM1<br>- To evaluate safety of T-DXd<br>- To evaluate pharmacokinetics (PK) of T-DXd <br>- To evaluate immunogenicity of T-DXd;Primary end point(s): - IDFS is defined as the time from randomization to invasive local, axillary or distant recurrence, invasive contralateral breast cancer, or death from any cause.<br>- IDFS will be determined based on disease recurrence per Investigator assessment based on all available clinical assessments.<br>;Timepoint(s) of evaluation of this end point: After at least 145 IDFS events are recorded for interim analysis and 207 IDFS events are recorded for final analysis
- Secondary Outcome Measures
Name Time Method