Clinical trial NCT05113251: Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Neoplasms
Breast Cancer
HER2-positive Early Breast Cancer
Keywords: Trastuzumab Trastuzumab Deruxtecan (T-DXd; DS-8201a)
DESTINY-BREAST11
Receptor, ErbB-2
breast neoplasms
Antineoplastic Agents, Phytogenic
Antineoplastic Agents;Molecular Mechanisms of Pharmacological Action
DB11
Enhertu
HER2 (human epidermal growth factor receptor 2)
breast cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2021-11-09
Enrollment: 927
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are assigned to one of three arms in parallel for the duration of the study.
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: rate of pathologic complete response (pCR)
timeFrame: Up to 39 months after study start
Secondary outcomes:
measure: Event-Free Survival
timeFrame: Up to 72 months after study start
measure: Invasive Disease-Free Survival (IDFS)
timeFrame: Up to 72 months after study start
measure: Overall Survival
timeFrame: Up to 72 months after study start
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Research Site
state: Arkansas
city: Beverly Hills
country: United States
facility: Research Site
state: California
city: Glendale
country: United States
facility: Research Site
state: California
city: Los Alamitos
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: East Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Summit
country: United States
facility: Research Site
state: New Jersey
city: Commack
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Ogden
country: United States
facility: Research Site
state: Utah
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Goiânia
country: Brazil
facility: Research Site
city: Ijuí
country: Brazil
facility: Research Site
city: Natal
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Panagyurishte
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec City
country: Canada
facility: Research Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Augsburg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Muenster
country: Germany
facility: Research Site
city: Mönchengladbach
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Paderborn
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Howrah
country: India
facility: Research Site
city: Nagpur
country: India
facility: Research Site
city: Nashik
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Raipur
country: India
facility: Research Site
city: Rishikesh
country: India
facility: Research Site
city: Surat
country: India
facility: Research Site
city: Thiruvananthapuram
country: India
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Candiolo
country: Italy
facility: Research Site
city: Livorno
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Naples
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Negrar
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Hidaka-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kawasaki-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Ota-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Bacolod
country: Philippines
facility: Research Site
city: Cebu City
country: Philippines
facility: Research Site
city: Davao City
country: Philippines
facility: Research Site
city: Iloilo
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: San Juan
country: Philippines
facility: Research Site
city: Biała Podlaska
country: Poland
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Koszalin
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Rzeszów
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Ar Riyāḑ
country: Saudi Arabia
facility: Research Site
city: Dammam
country: Saudi Arabia
facility: Research Site
city: Jeddah
country: Saudi Arabia
facility: Research Site
city: Jeddah
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Vigo
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
Study officials:
References: