Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase 3 Open-label Trial of Neoadjuvant Trastuzumab Deruxtecan (T-DXd) Monotherapy or T-DXd Followed by THP Compared to ddAC-THP in Participants With High-risk HER2-positive Early-stage Breast Cancer (DESTINY-Breast11)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05113251
• Other study ID #: D967RC00001
• Secondary ID: 2021-000603-21
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 25, 2021
• Est. completion date: April 30, 2027

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will look at the efficacy and safety of trastuzumab deruxtecan (T-DXd) in a neoadjuvant setting, in high-risk, HER2-positive early non-metastatic breast cancer.

Description:

The target population of interest in this study is participants with high-risk HER2-positive early-stage breast cancer. The purpose of this study is to determine the efficacy and safety of T-DXd neoadjuvant therapy.

Participants will be randomised to one of 3 arms: T-DXd monotherapy (Arm A), T-DXd followed by THP (Arm B), or ddAC-THP (Arm C).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 912
• Est. completion date: April 30, 2027
• Est. primary completion date: December 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Patients must be at least 18 years of age.

• Histologically documented HER2-positive early breast cancer (EBC) participants, including 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

• ECOG performance status of 0 or 1 at randomization

• Adequate organ and bone marrow function

• LVEF = 50% within 28 days before randomization

• 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

Exclusion Criteria:

• prior history of invasive breast cancer

• stage IV breast cancer (determined by AJCC staging system)

• any primary malignancy within 3 years (except resected non-melanoma skin cancer, curatively treated in situ disease) Note: This includes a second current breast primary malignancy (ie, bilateral breast cancer)

• history of DCIS (except those treated with mastectomy >5 years prior to current diagnosis)

• History of, or current, ILD/pneumonitis

• Prior systemic therapy for the treatment of breast cancer

• Previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• HER2-positive Early Breast Cancer

Intervention

Drug:
• Trastuzumab Deruxtecan
administered by intravenous infusion
• Paclitaxel
administered by intravenous infusion
• Trastuzumab
administered by intravenous infusion
• Pertuzumab
administered by intravenous infusion
• Doxorubicin
administered by intravenous infusion
• cyclophosphamide
administered by intravenous infusion

Locations

Country	Name	City	State
Brazil	Research Site	Goiânia
Brazil	Research Site	Ijuí
Brazil	Research Site	Natal
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Panagyurishte
Bulgaria	Research Site	Sofia
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Kunming
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Zhengzhou
Germany	Research Site	Augsburg
Germany	Research Site	Berlin
Germany	Research Site	Erlangen
Germany	Research Site	Hamburg
Germany	Research Site	Heidelberg
Germany	Research Site	Kiel
Germany	Research Site	Leipzig
Germany	Research Site	Mönchengladbach
Germany	Research Site	Muenster
Germany	Research Site	München
Germany	Research Site	Paderborn
Germany	Research Site	Tübingen
India	Research Site	Gurgaon
India	Research Site	Howrah
India	Research Site	Nagpur
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Raipur
India	Research Site	Rishikesh
India	Research Site	Surat
India	Research Site	Thiruvananthapuram
Italy	Research Site	Bologna
Italy	Research Site	Candiolo
Italy	Research Site	Livorno
Italy	Research Site	Milano
Italy	Research Site	Naples
Italy	Research Site	Napoli
Italy	Research Site	Negrar
Italy	Research Site	Padova
Italy	Research Site	Rome
Italy	Research Site	Rozzano
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Hidaka-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Ota-shi
Japan	Research Site	Shinjuku-ku
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Bacolod
Philippines	Research Site	Cebu City
Philippines	Research Site	Davao City
Philippines	Research Site	Iloilo
Philippines	Research Site	Quezon City
Philippines	Research Site	San Juan
Poland	Research Site	Biala Podlaska
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Koszalin
Poland	Research Site	Lublin
Poland	Research Site	Rzeszów
Poland	Research Site	Warszawa
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Saudi Arabia	Research Site	Ar Riya?
Saudi Arabia	Research Site	Dammam
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Riyadh
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
Spain	Research Site	Vigo
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei 112
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
United States	Research Site	Beverly Hills	California
United States	Research Site	Commack	New York
United States	Research Site	Durham	North Carolina
United States	Research Site	East Brunswick	New Jersey
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Fort Worth	Texas
United States	Research Site	Germantown	Tennessee
United States	Research Site	Glendale	California
United States	Research Site	Greenville	South Carolina
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lexington	Kentucky
United States	Research Site	Los Alamitos	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	Ogden	Utah
United States	Research Site	Orange	California
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Springdale	Arkansas
United States	Research Site	Summit	New Jersey
United States	Research Site	Tacoma	Washington

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Canada,  China,  Germany,  India,  Italy,  Japan,  Korea, Republic of,  Peru,  Philippines,  Poland,  Russian Federation,  Saudi Arabia,  Spain,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rate of pathologic complete response (pCR)	Proportion of participants who have no evidence by H&E staining of residual invasive disease	Up to 39 months after study start
Secondary	Event-Free Survival		Up to 72 months after study start
Secondary	Invasive Disease-Free Survival (IDFS)		Up to 72 months after study start
Secondary	Overall Survival		Up to 72 months after study start