A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer
A Phase III, Open-label, Randomised Study of Neoadjuvant Datopotamab Deruxtecan (Dato-DXd) Plus Durvalumab Followed by Adjuvant Durvalumab With or Without Chemotherapy Versus Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab With or Without Chemotherapy for the Treatment of Adult Patients With Previously Untreated Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer (D926QC00001; TROPION-Breast04)
2 other identifiers
interventional
1,902
25 countries
282
Brief Summary
This is a Phase III, 2-arm, randomised, open-label, multicentre, global study assessing the efficacy and safety of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy compared with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 breast-cancer
Started Nov 2023
Typical duration for phase_3 breast-cancer
282 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 12, 2023
CompletedFirst Posted
Study publicly available on registry
November 1, 2023
CompletedStudy Start
First participant enrolled
November 14, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 20, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 23, 2032
April 2, 2026
March 1, 2026
5 years
October 12, 2023
April 1, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Event-free survival (EFS) in the experimental vs control arms
EFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: disease progression precluding surgery, disease recurrence (local, regional, distant, or contralateral), second primary invasive cancer (other than squamous or basal cell skin cancer), or relapse from prior malignancy, or death by any cause (in the absence of recurrence). Non-invasive breast cancers and positive margins in the surgical sample do not count as an event for EFS. EFS will be determined by the investigator based on all available clinical assessments. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the Hazard Ratio of EFS.
Date of randomization to date of the EFS event, up to 93 months after the first subject randomized
Secondary Outcomes (12)
Pathologic Complete Response (pCR) in the experimental vs control arms
At the time of definitive surgery
Overall Survival (OS) in the experimental vs control arms
Date of randomization to date of death due to any cause, up to 108 months after the first subject randomized
Distant disease-free survival (DDFS) in the experimental vs control arms
Date of randomization to date of the DDFS event, up to 93 months after the first subject randomized
Participant-reported breast and arm symptoms in the experimental vs. control arms
From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first.
Participant-reported physical function in the experimental vs. control arms
From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).
- +7 more secondary outcomes
Study Arms (2)
Dato-DXd plus durvalumab
EXPERIMENTALParticipants receive durvalumab every 3 weeks (Q3W) + Dato-DXd Q3W as neoadjuvant therapy prior to surgery; followed by 9 cycles of durvaluamb Q3W as adjuvant therapy post-surgery. Adjuvant chemotherapy may be given in combination with durvalumab only if participants have residual disease. Olaparib may be given for participants with gBRCA-positive tumours and residual disease Adjuvant chemotherapy may be one of these: 1. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) and carboplatin (weekly or Q3W) for 4 cycles (12 weeks); 2. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) for 4 cycles (12 weeks); 3. Carboplatin (weekly or Q3W) + paclitaxel (weekly) for 4 cycles (12 weeks); 4. Capecitabine (Q3W) for 8 cycles.
Pembrolizumab plus chemotherapy
ACTIVE COMPARATORParticipants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Adjuvant capecitabine (Q3W) for 8 cycles may be given in combination with pembrolizumab only if participants have residual disease. Olaparib may be given for participants with gBRCA-positive tumours and residual disease.
Interventions
IV infusion Experimental/Active Comparator
IV infusion Experimental/Active Comparator
IV infusion Experimental/Active Comparator
Tablet Oral route of administration Experimental/Active Comparator
Tablet Oral route of administration Experimental/Active Comparator
Experimental drug IV infusion
IV Infusion Active comparator
IV infusion Experimental/Active Comparator
IV Infusion Experimental/Active Comparator
Eligibility Criteria
You may qualify if:
- Participant must be ≥ 18 years, at the time of signing the ICF.
- Histologically confirmed Stage II or III unilateral or bilateral primary invasive TNBC or hormone receptor-low/HER2-negative breast cancer
- ECOG PS of 0 or 1
- Provision of acceptable tumor sample
- Adequate bone marrow reserve and organ function
- Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and aligned with protocol requirements.
You may not qualify if:
- History of any prior invasive breast malignancy
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 5 years before randomization.
- active or prior documented autoimmune or inflammatory disorders.
- Evidence of distant disease.
- Clinically significant corneal disease.
- Has active or uncontrolled hepatitis B or C virus infection.
- Known HIV infection that is not well controlled.
- Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections; or inability to rule out infections.
- Known to have active tuberculosis infection
- Mean resting corrected QTcF interval \> 470 ms obtained from ECG
- Uncontrolled or significant cardiac disease.
- History of non-infectious ILD/pneumonitis
- Has severe pulmonary function compromise
- Any prior or concurrent surgery, radiotherapy or systemic anticancer therapy for TNBC or hormone receptor-low/HER2-negative breast cancer
- For females only: is pregnant (confirmed with positive serum pregnancy test) or breastfeeding, or planning to become pregnant.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyocollaborator
Study Sites (283)
Research Site
Daphne, Alabama, 36526, United States
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Prescott, Arizona, 86301, United States
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Jonesboro, Arkansas, 72401, United States
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Rogers, Arkansas, 72758, United States
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Los Angeles, California, 90033, United States
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Santa Barbara, California, 93105, United States
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Santa Rosa, California, 92805, United States
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Torrance, California, 90505, United States
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Aurora, Colorado, 80045, United States
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Longmont, Colorado, 80504, United States
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Bridgeport, Connecticut, 06606, United States
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New Haven, Connecticut, 06510, United States
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Fort Myers, Florida, 33901, United States
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Jacksonville, Florida, 32256, United States
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St. Petersburg, Florida, 33705, United States
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West Palm Beach, Florida, 33401, United States
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Atlanta, Georgia, 30342, United States
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Des Moines, Iowa, 50309, United States
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Edgewood, Kentucky, 41017, United States
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Louisville, Kentucky, 40202, United States
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Baton Rouge, Louisiana, 70817, United States
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Annapolis, Maryland, 21401, United States
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Boston, Massachusetts, 02215, United States
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Grand Rapids, Michigan, 49503, United States
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Traverse City, Michigan, 49684, United States
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Burnsville, Minnesota, 55337, United States
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Minneapolis, Minnesota, 55407, United States
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Columbia, Missouri, 65212, United States
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Omaha, Nebraska, 68130, United States
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East Brunswick, New Jersey, 08816, United States
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New Brunswick, New Jersey, 08901, United States
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Santa Fe, New Mexico, 87505, United States
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New York, New York, 10065, United States
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Charlotte, North Carolina, 28204, United States
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Durham, North Carolina, 27710, United States
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Winston-Salem, North Carolina, 27103, United States
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Blue Ash, Ohio, 45242, United States
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Eugene, Oregon, 97401, United States
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Portland, Oregon, 97223, United States
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Philadelphia, Pennsylvania, 19104, United States
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Pittsburgh, Pennsylvania, 15212, United States
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Chattanooga, Tennessee, 37404, United States
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Nashville, Tennessee, 37203, United States
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Austin, Texas, 78731, United States
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Dallas, Texas, 75231, United States
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Dallas, Texas, 75235, United States
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Dallas, Texas, 75390-8843, United States
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El Paso, Texas, 79902, United States
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Flower Mound, Texas, 75028, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77030, United States
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San Antonio, Texas, 78240, United States
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Webster, Texas, 77598, United States
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Fairfax, Virginia, 22031, United States
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Norfolk, Virginia, 23502, United States
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Roanoke, Virginia, 24014, United States
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Winchester, Virginia, 22601, United States
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Tacoma, Washington, 98405, United States
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East Melbourne, 3002, Australia
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Feldkirch, 6807, Austria
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Innsbruck, 6020, Austria
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Linz, 4010, Austria
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Salzburg, 5020, Austria
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Antwerp, 2020, Belgium
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Brasschaat, 2930, Belgium
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Charleroi, 6060, Belgium
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Libramont-Chevigny, 6800, Belgium
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Brasília, 71681-603, Brazil
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Curitiba, 80440-220, Brazil
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Fortaleza, 60336-045, Brazil
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Londrina, 86015-520, Brazil
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Natal, 59075-740, Brazil
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Porto Alegre, 90035-000, Brazil
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Porto Alegre, 90035-903, Brazil
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Ribeirão Preto, 14051-140, Brazil
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Santo André, 09060-650, Brazil
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São Paulo, 01246-000, Brazil
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Taubaté, 12030-200, Brazil
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Vitória, 29043-260, Brazil
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Shumen, 9700, Bulgaria
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Sofia, 1330, Bulgaria
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Sofia, Bulgaria
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Calgary, Alberta, T2N 5G2, Canada
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Vancouver, British Columbia, VSZ 4E6, Canada
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Barrie, Ontario, L4M 6M2, Canada
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London, Ontario, N6A 5W9, Canada
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Oshawa, Ontario, L1G 2B9, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Lévis, Quebec, G6V 3Z1, Canada
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Montreal, Quebec, H1T 2M4, Canada
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Montreal, Quebec, H2X 0C1, Canada
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Montreal, Quebec, H4A-3J1, Canada
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Saint-Jérôme, Quebec, J7Z 5T3, Canada
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Sherbrooke, Quebec, J1H 5N4, Canada
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Montreal, H3T 1E2, Canada
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Ottawa, K1H 8L6, Canada
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Beijing, 100044, China
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Bengbu, 233004, China
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Changchun, 130021, China
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Changsha, 410008, China
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Chengdu, 610000, China
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Guangzhou, 510060, China
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Guangzhou, 510120, China
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Hangzhou, 310009, China
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Hangzhou, 310022, China
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Harbin, 150049, China
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Jinan, 250117, China
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Linhai, 317000, China
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Nanchang, 330009, China
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Nanchang, 330029, China
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Nanjing, 210008, China
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Nanning, 530021, China
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Shanghai, 200025, China
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Shenyang, 110004, China
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Shijiazhuang, 050020, China
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Suining, 629000, China
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Tianjin, 300000, China
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Wuhan, 430022, China
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Xi'an, 710061, China
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Xintai, 54031, China
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Zhaoqing, 526000, China
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Zhengzhou, 450008, China
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Avignon, 84918, France
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Bayonne, 64100, France
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Caen, 41076, France
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Clermont-Ferrand, 63011, France
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Limoges, 87000, France
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Marseille, 13273, France
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Montpellier, 34298, France
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Nice, 06100, France
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Paris, 75010, France
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Reims, 51056, France
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Toulouse, 31100, France
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Vandœuvre-lès-Nancy, 54519, France
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Villejuif, 94805, France
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Augsburg, 86150, Germany
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Berlin, 10967, Germany
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Berlin, 13125, Germany
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Dessau, 06847, Germany
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Dresden, 01307, Germany
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Erlangen, 91054, Germany
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Essen, 45130, Germany
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Esslingen am Neckar, 73730, Germany
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Frankfurt am Main, 60431, Germany
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Freiburg im Breisgau, 79110, Germany
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Hamburg, 20246, Germany
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Hanover, 30559, Germany
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Heidelberg, 69120, Germany
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Kiel, 24105, Germany
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Mainz, 55131, Germany
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Mannheim, 68167, Germany
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München, 80637, Germany
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Münster, 48149, Germany
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Trier, 54290, Germany
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Ulm, 89075, Germany
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Hong Kong, 999077, Hong Kong
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Budapest, 1122, Hungary
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Kecskemét, 6000, Hungary
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Miskolc, 3526, Hungary
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Szekszárd, 7100, Hungary
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Bengaluru, 560085, India
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Delhi, 110029, India
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Delhi, 110085, India
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Kolkata, 700016, India
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Kolkata, 700099, India
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Marg Jaipur, 302004, India
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Nagpur, 440001, India
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Nashik, 422011, India
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Thiruvananthapuram, 695011, India
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Vadodara, 391760, India
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Empoli, 50053, Italy
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Lucca, 55100, Italy
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Macerata, 62100, Italy
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Milan, 20132, Italy
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Modena, 41124, Italy
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Naples, 80131, Italy
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Padua, 35128, Italy
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Roma, 00168, Italy
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Rozzano, 20089, Italy
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Torino, 10126, Italy
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Tricase, 73039, Italy
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Udine, 33100, Italy
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Akashi-shi, 673-8558, Japan
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Akita, 010-8543, Japan
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Bunkyō City, 113-8431, Japan
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Chiba, 260-8717, Japan
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Chūōku, 104-0045, Japan
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Chūōku, 104-8560, Japan
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Fukuoka, 811-1395, Japan
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Fukushima, 960-1295, Japan
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Gifu, 501-1194, Japan
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Hidaka-shi, 350-1298, Japan
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Hirakata-shi, 573-1191, Japan
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Hiroshima, 730-0011, Japan
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Hiroshima, 734-8551, Japan
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Isehara-shi, 259-1193, Japan
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Kashiwa, 227-8577, Japan
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Kumamoto, 860-8556, Japan
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Kurume-shi, 830-0011, Japan
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Kyoto, 606-8507, Japan
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Matsuyama, 791-0280, Japan
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Nagoya, 460-0001, Japan
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Nagoya, 466-8560, Japan
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Nagoya, 467-0001, Japan
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Niigata, 951-8566, Japan
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Okayama, 700-8558, Japan
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Osaka, 541-8567, Japan
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Sapporo, 003-0804, Japan
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Sapporo, 060-8648, Japan
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Sendai, 980-8574, Japan
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Shinagawa-ku, 142-8666, Japan
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Shinjuku-ku, 160-0023, Japan
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Shinjuku-ku, 162-8655, Japan
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Sunto-gun, 411-8777, Japan
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Tsu, 514-8507, Japan
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Yokohama, 241-8515, Japan
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George Town, 10990, Malaysia
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Kuala Lumpur, 50586, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Kuala Selangor, 62250, Malaysia
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Kuching, 93586, Malaysia
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Bialystok, 15-027, Poland
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Bydgoszcz, 85-796, Poland
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Gdynia, 81-519, Poland
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Krakow, 31-501, Poland
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Lodz, 93-338, Poland
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Warsaw, 02-781, Poland
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Singapore, 168583, Singapore
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Daegu, 41404, South Korea
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Goyang-si, 10408, South Korea
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Seongnam, 13620, South Korea
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Seoul, 02841, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06273, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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Barcelona, 08036, Spain
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Granada, 18016, Spain
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Hospitalet deLlobregat, 08907, Spain
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Madrid, 28007, Spain
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Madrid, 28034, Spain
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Santiago de Compostela, 15706, Spain
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Seville, 41009, Spain
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Zaragoza, 50009, Spain
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Baden, CH-5405, Switzerland
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Basel, 4031, Switzerland
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Bern, 3010, Switzerland
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Frauenfeld, 8501, Switzerland
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Changhua, 500, Taiwan
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Kaohsiung City, 82445, Taiwan
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Taichung, 40447, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 10449, Taiwan
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Taipei, 112, Taiwan
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Taoyuan District, 333, Taiwan
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Bangkok, 10210, Thailand
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Bangkok, 10330, Thailand
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Dusit, 10300, Thailand
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Muang, 50200, Thailand
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Songkhla, 90110, Thailand
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Adapazarı, 54290, Turkey (Türkiye)
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Ankara, 06010, Turkey (Türkiye)
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Ankara, 06340, Turkey (Türkiye)
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Ankara, 06520, Turkey (Türkiye)
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Istanbul, 34722, Turkey (Türkiye)
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Kayseri, 38039, Turkey (Türkiye)
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Samsun, 55200, Turkey (Türkiye)
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Birmingham, B15 2TG, United Kingdom
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Cardiff, CF14 2TL, United Kingdom
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Lancaster, LA1 4RP, United Kingdom
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London, EC1A 7BE, United Kingdom
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Northampton, NN1 5BD, United Kingdom
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Oxford, OX3 7LE, United Kingdom
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Taunton, TA1 5DA, United Kingdom
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Hanoi, 100000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
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Hồ Chí Minh, 700000, Vietnam
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Vinh, 460000, Vietnam
Related Publications (1)
McArthur HL, Tolaney SM, Dent R, Schmid P, Asselah J, Liu Q, Meisel JL, Niikura N, Park YH, Werutsky G, Bianchini G, Andersen JC, Kozarski R, Rokutanda N, Pistilli B, Loibl S. TROPION-Breast04: a randomized phase III study of neoadjuvant datopotamab deruxtecan (Dato-DXd) plus durvalumab followed by adjuvant durvalumab versus standard of care in patients with treatment-naive early-stage triple negative or HR-low/HER2- breast cancer. Ther Adv Med Oncol. 2025 Feb 5;17:17588359251316176. doi: 10.1177/17588359251316176. eCollection 2025.
PMID: 39917260DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 12, 2023
First Posted
November 1, 2023
Study Start
November 14, 2023
Primary Completion (Estimated)
November 20, 2028
Study Completion (Estimated)
September 23, 2032
Last Updated
April 2, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- 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 rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (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.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure