Japanease

Dec. 01, 2020

Mar. 25, 2021

jRCT2061200033

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

T-DXd vs. T-DM1 in high-risk HER2-positive patients with residual invasive breast cancer following neoadjuvant therapy

Nagao Kiminori

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Dec. 04, 2020

1600

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

United States of America/Argentina/Australia/Belgium/Brazil/Canada/Chile/China/Czechia/Denmark/France/Germany/Greece/Hong Kong/Ireland/Israel/Italy/South Korea/Mexico/Netherlands/Peru/Poland/Portugal/Romania/Russian Federation/Singapore/Spain/Taiwan/Turkey/United Kingdom

- Adults >=18 years old. (Follow local regulatory requirements if the legal age of consent for study participation is >18 years old.)
- Pathologically documented HER2-positive BC:
- HER2-positive expression defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) confirmed prior to study randomization.
- Histologically confirmed invasive breast carcinoma.
- Clinical stage at disease presentation: T1-4, N0-3, M0 (Note: Patients presenting with T1N0 tumors will not be 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.
- 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.
- 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.
- Adequate excision as confirmed per medical records: surgical removal of all clinically evident disease in the breast and lymph nodes.
- An interval of no more than 12 weeks between the date of last surgery and the date of randomization.
- Known 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.
- Left ventricular ejection fraction (LVEF) >=50% within 28 days prior to randomization.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.
- Has adequate organ function within 14 days before randomization.

- 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)
- 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
- History of other malignancy within the last 5 years except for appropriately treated CIS of the cervix, non-melanoma skin carcinoma, Stage I melanoma skin carcinoma, Stage I uterine cancer, or other appropriately treated non-breast malignancies.
- 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 with pulmonary involvement (eg, Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior lobectomy or pneumonectomy.
- 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.

20age old over
No limit

Both

HER2-Positive Primary Breast Cancer, Residual Invasive Breast Cancer

Experimental: Trastuzumab deruxtecan (T-DXd)
Participants who will be randomized to receive trastuzumab deruxtecan (T-DXd) at a starting dose of 5.4 mg/kg. Administered initially as an intravenous (IV) infusion at a dose of 5.4 mg/kg on Day 1 of each 21-day cycle.

Active Comparator: Trastuzumab ematansine (T-DM1)
Participants who will be randomized to receive trastuzumab ematansine (T-DM1) at a starting dose of 3.6 mg/kg. Administered initially as an intravenous (IV) infusion at a dose of 3.6 mg/kg on Day 1 of each 21-day cycle.

Invasive Disease-free Survival (IDFS) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment

- Disease-free Survival (DFS) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
- Overall Survival (OS) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
- Distant Recurrence-free Interval (DRFI) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
- Brain Metastases-free Interval (BMFI) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
- Percentage of Treatment-emergent Adverse Events in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
- Serum Concentrations of Trastuzumab Deruxtecan (T-DXd), total anti-HER2 antibody, and Active Metabolite MAAA-1181a
- Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd)

Recruiting

DAIICHI SANKYO Co.,Ltd.
AstraZeneca
Applicable
IRB of Okayama University Hospital
2-5-1 Shikata-cho, Kita-ku,Okayama-city, Okayama

+81-86-223-7151

chiken@okayama-u.ac.jp
Approval

Oct. 21, 2020

Yes

Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Documents: - Study Protocol - Statistical Analysis Plan - Clinical Study Report Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

NCT04622319
ClinicalTrials.gov
2020-003982-20
EU Clinical Trials Register (EU-CTR)