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

August 10, 2026 updated by: AstraZeneca

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)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

927

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Goiânia, Brazil, 74000-000
        • Research Site
      • Ijuí, Brazil, 98700-000
        • Research Site
      • Natal, Brazil, 59075-740
        • Research Site
      • Porto Alegre, Brazil, 90610-000
        • Research Site
      • Porto Alegre, Brazil, 91350-200
        • Research Site
      • São Paulo, Brazil, 01221-020
        • Research Site
      • São Paulo, Brazil, 01229-010
        • Research Site
  • Bulgaria
      • Panagyurishte, Bulgaria, 4500
        • Research Site
      • Sofia, Bulgaria, 1330
        • Research Site
  • Canada
      • Montreal, Canada, H3T 1E2
        • Research Site
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Research Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X5
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H4A-3J1
        • Research Site
      • Québec, Quebec, Canada, G1S 4L8
        • Research Site
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Research Site
  • China
      • Beijing, China, 100039
        • Research Site
      • Changsha, China, 410013
        • Research Site
      • Changsha, China, 410008
        • Research Site
      • Chongqing, China, 400030
        • Research Site
      • Guangzhou, China, 510080
        • Research Site
      • Guangzhou, China, 510060
        • Research Site
      • Guangzhou, China, 510700
        • Research Site
      • Kunming, China, 650118
        • Research Site
      • Nanning, China, 530021
        • Research Site
      • Qingdao, China, 266100
        • Research Site
      • Shanghai, China, 200032
        • Research Site
      • Shenyang, China, 110001
        • Research Site
      • Tianjin, China, 300060
        • Research Site
      • Wuhan, China, 430079
        • Research Site
      • Wuhan, China, 430060
        • Research Site
      • Zhengzhou, China, 450008
        • Research Site
  • Germany
      • Augsburg, Germany, 86156
        • Research Site
      • Berlin, Germany, 10117
        • Research Site
      • Erlangen, Germany, 91054
        • Research Site
      • Hamburg, Germany, 20357
        • Research Site
      • Heidelberg, Germany, 69120
        • Research Site
      • Kiel, Germany, 24105
        • Research Site
      • Leipzig, Germany, 4103
        • Research Site
      • Mönchengladbach, Germany, 41061
        • Research Site
      • München, Germany, 81377
        • Research Site
      • Münster, Germany, 48149
        • Research Site
      • Paderborn, Germany, 33098
        • Research Site
      • Tübingen, Germany, 72076
        • Research Site
  • India
      • Gurgaon, India, 122001
        • Research Site
      • Howrah, India, 711103
        • Research Site
      • Nagpur, India, 440001
        • Research Site
      • Nashik, India, 422002
        • Research Site
      • New Delhi, India, 110 085
        • Research Site
      • New Delhi, India, 110029
        • Research Site
      • Raipur, India, 492001
        • Research Site
      • Rishikesh, India, 249203
        • Research Site
      • Surat, India, 395002
        • Research Site
      • Thiruvananthapuram, India, 695011
        • Research Site
  • Italy
      • Bologna, Italy, 40138
        • Research Site
      • Candiolo, Italy, 10060
        • Research Site
      • Livorno, Italy, 57100
        • Research Site
      • Milan, Italy, 20132
        • Research Site
      • Naples, Italy, 80131
        • Research Site
      • Negrar, Italy, 37024
        • Research Site
      • Padova, Italy, 35128
        • Research Site
      • Roma, Italy, 00168
        • Research Site
      • Rozzano, Italy, 20089
        • Research Site
  • Japan
      • Chūōku, Japan, 104-8560
        • Research Site
      • Chūōku, Japan, 862-8655
        • Research Site
      • Hidaka-shi, Japan, 350-1298
        • Research Site
      • Hiroshima, Japan, 734-8551
        • Research Site
      • Kawasaki-shi, Japan, 216-8511
        • Research Site
      • Kōtoku, Japan, 135-8550
        • Research Site
      • Nagoya, Japan, 466-8560
        • Research Site
      • Nagoya, Japan, 467-8602
        • Research Site
      • Ota-shi, Japan, 373-8550
        • Research Site
      • Shinjuku-ku, Japan, 162-8655
        • Research Site
  • Peru
      • Lima, Peru, 15033
        • Research Site
      • Lima, Peru, LIMA 34
        • Research Site
      • Lima, Peru, LIMA 29
        • Research Site
      • Lima, Peru, Lima 32
        • Research Site
  • Philippines
      • Bacolod, Philippines, 6100
        • Research Site
      • Cebu City, Philippines, 6000
        • Research Site
      • Davao City, Philippines, 8000
        • Research Site
      • Iloilo City, Philippines, 5000
        • Research Site
      • Quezon City, Philippines, 1112
        • Research Site
      • San Juan City, Philippines
        • Research Site
  • Poland
      • Bialystok, Poland, 15-027
        • Research Site
      • Biała Podlaska, Poland, 21-500
        • Research Site
      • Bydgoszcz, Poland, 85-796
        • Research Site
      • Koszalin, Poland, 75-581
        • Research Site
      • Lublin, Poland, 20-090
        • Research Site
      • Rzeszów, Poland, 30-055
        • Research Site
      • Warsaw, Poland, 02-781
        • Research Site
  • Russia
      • Moscow, Russia, 117997
        • Research Site
      • Moscow, Russia, 143423
        • Research Site
      • Saint Petersburg, Russia, 197758
        • Research Site
      • Saint Petersburg, Russia, 190020
        • Research Site
  • Saudi Arabia
      • Dammam, Saudi Arabia, 31444
        • Research Site
      • Jeddah, Saudi Arabia, 21423
        • Research Site
      • Jeddah, Saudi Arabia, 23214
        • Research Site
      • Riyadh, Saudi Arabia, 11426
        • Research Site
      • Riyadh, Saudi Arabia, 3354
        • Research Site
  • South Korea
      • Goyang-si, South Korea, 10408
        • Research Site
      • Seoul, South Korea, 03080
        • Research Site
      • Seoul, South Korea, 03722
        • Research Site
      • Seoul, South Korea, 05505
        • Research Site
      • Seoul, South Korea, 06273
        • Research Site
      • Seoul, South Korea, 06351
        • Research Site
  • Spain
      • Barcelona, Spain, 08035
        • Research Site
      • Barcelona, Spain, 08028
        • Research Site
      • Madrid, Spain, 28040
        • Research Site
      • Madrid, Spain, 28007
        • Research Site
      • Seville, Spain, 41013
        • Research Site
      • Vigo, Spain, 36312
        • Research Site
  • Taiwan
      • Kaohsiung City, Taiwan, 82445
        • Research Site
      • Taichung, Taiwan, 40443
        • Research Site
      • Tainan, Taiwan, 710
        • Research Site
      • Taipei, Taiwan, 100
        • Research Site
      • Taipei, Taiwan, 11217
        • Research Site
      • Taipei, Taiwan, 114
        • Research Site
      • Taoyuan, Taiwan, 333
        • Research Site
  • Thailand
      • Bangkok, Thailand, 10210
        • Research Site
      • Bangkok, Thailand, 10330
        • Research Site
      • Bangkok, Thailand, 10400
        • Research Site
      • Chiang Mai, Thailand, 50200
        • Research Site
      • Hat Yai, Thailand, 90110
        • Research Site
      • Khon Kaen, Thailand, 40002
        • Research Site
  • United States
    • Arkansas
      • Springdale, Arkansas, United States, 72762
        • Research Site
    • California
      • Beverly Hills, California, United States, 90211
        • Research Site
      • Glendale, California, United States, 91204
        • Research Site
      • Los Alamitos, California, United States, 90720
        • Research Site
      • Orange, California, United States, 92868
        • Research Site
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Research Site
    • Indiana
      • Fort Wayne, Indiana, United States, 46804
        • Research Site
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Research Site
      • Louisville, Kentucky, United States, 40202
        • Research Site
    • Louisiana
      • Shreveport, Louisiana, United States, 71101
        • Research Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Research Site
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Research Site
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Research Site
      • Summit, New Jersey, United States, 07901
        • Research Site
    • New York
      • Commack, New York, United States, 11725
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site
    • South Carolina
      • Greenville, South Carolina, United States, 29607
        • Research Site
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Research Site
      • Nashville, Tennessee, United States, 37203
        • Research Site
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Research Site
    • Utah
      • Ogden, Utah, United States, 84405
        • Research Site
    • Washington
      • Tacoma, Washington, United States, 98405
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Trastuzumab deruxtecan
Drug: Trastuzumab Deruxtecan
administered by intravenous infusion
Other Names:
  • Enhertu
  • T-DXd
Experimental: Arm B
T-DXd, followed by THP
Drug: Trastuzumab Deruxtecan
administered by intravenous infusion
Other Names:
  • Enhertu
  • T-DXd
Drug: Paclitaxel
administered by intravenous infusion
Other Names:
  • Taxol
  • Onxol
Drug: Trastuzumab
administered by intravenous infusion
Other Names:
  • Herceptin
  • Herzuma
Drug: Pertuzumab
administered by intravenous infusion
Other Names:
  • Perjeta
Active Comparator: Arm C
doxorubicin and cyclophosphamide, followed by THP
Drug: Paclitaxel
administered by intravenous infusion
Other Names:
  • Taxol
  • Onxol
Drug: Trastuzumab
administered by intravenous infusion
Other Names:
  • Herceptin
  • Herzuma
Drug: Pertuzumab
administered by intravenous infusion
Other Names:
  • Perjeta
Drug: Doxorubicin
administered by intravenous infusion
Other Names:
  • Adriamycin
  • Rubex
Drug: cyclophosphamide
administered by intravenous infusion
Other Names:
  • Cytoxan
  • Neosar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Pathologic Complete Response (pCR).
Time Frame: Through to definitive surgery or discontinuation/withdrawal from study, up to a maximum of approximately 40 months from randomization to primary pCR DCO (12MAR2025)
Proportion of participants who have no evidence by Hematoxylin & Eosin (H&E) staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy.
Through to definitive surgery or discontinuation/withdrawal from study, up to a maximum of approximately 40 months from randomization to primary pCR DCO (12MAR2025)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-Free Survival (Count)
Time Frame: Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027)
Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause.
Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027)
Event-Free Survival (Duration)
Time Frame: Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027)
Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause.
Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Collaborators

Daiichi Sankyo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 25, 2021

Primary Completion (Actual)

March 12, 2025

Study Completion (Estimated)

April 30, 2027

Study Registration Dates

First Submitted

October 22, 2021

First Submitted That Met QC Criteria

November 8, 2021

First Posted (Actual)

November 9, 2021

Study Record Updates

Last Update Posted (Actual)

August 11, 2026

Last Update Submitted That Met QC Criteria

August 10, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D967RC00001
  • 2021-000603-21 (EudraCT Number)
  • 2023-505210-18-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient data from AstraZeneca Group of Companies, sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ Disclosure Commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Access Criteria

When a request has been approved, AstraZeneca will provide access to the de-identified patient level data in an approved sponsor tool. Signed Data Sharing Agreements (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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