Breast CancerPhase 3NCT06112379
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 3 study testing Dato-DXd, Durvalumab and Pembrolizumab in people with Breast Cancer, run by AstraZeneca at 283 sites in 26 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Dato-DXd, Durvalumab and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,902 participants
- Where
- 283 sitesin 26 countries
- Study dates
- 14 Nov 2023to 23 Sep 2032
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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.
- Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of study intervention, or as dictated by local PI for SoC if longer.
- Concurrent use of systemic hormone replacement therapy or oral hormonal contraception
Trial locations and contacts
283 sites in 26 countries.
283 sites in 26 countries
United States58 sites
Research Site
Annapolis, Maryland, 21401
Research Site
Atlanta, Georgia, 30342
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Aurora, Colorado, 80045
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Austin, Texas, 78731
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Baton Rouge, Louisiana, 70817
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Blue Ash, Ohio, 45242
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Boston, Massachusetts, 02215
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Bridgeport, Connecticut, 06606
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Burnsville, Minnesota, 55337
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Charlotte, North Carolina, 28204
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Chattanooga, Tennessee, 37404
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Columbia, Missouri, 65212
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Dallas, Texas, 75231
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Dallas, Texas, 75235
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Dallas, Texas, 75390-8843
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Daphne, Alabama, 36526
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Des Moines, Iowa, 50309
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Durham, North Carolina, 27710
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East Brunswick, New Jersey, 08816
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Edgewood, Kentucky, 41017
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El Paso, Texas, 79902
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Eugene, Oregon, 97401
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Fairfax, Virginia, 22031
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Flower Mound, Texas, 75028
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Fort Myers, Florida, 33901
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Fort Worth, Texas, 76104
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Grand Rapids, Michigan, 49503
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Houston, Texas, 77030
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Jacksonville, Florida, 32256
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Jonesboro, Arkansas, 72401
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Longmont, Colorado, 80504
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Los Angeles, California, 90033
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Louisville, Kentucky, 40202
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Minneapolis, Minnesota, 55407
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Nashville, Tennessee, 37203
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New Brunswick, New Jersey, 08901
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New Haven, Connecticut, 06510
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New York, New York, 10065
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Norfolk, Virginia, 23502
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Omaha, Nebraska, 68130
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Philadelphia, Pennsylvania, 19104
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Pittsburgh, Pennsylvania, 15212
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Portland, Oregon, 97223
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Prescott, Arizona, 86301
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Roanoke, Virginia, 24014
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Rogers, Arkansas, 72758
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San Antonio, Texas, 78240
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Santa Barbara, California, 93105
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Santa Fe, New Mexico, 87505
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Santa Rosa, California, 92805
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St. Petersburg, Florida, 33705
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Tacoma, Washington, 98405
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Torrance, California, 90505
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Traverse City, Michigan, 49684
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Webster, Texas, 77598
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West Palm Beach, Florida, 33401
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Winchester, Virginia, 22601
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Winston-Salem, North Carolina, 27103
Japan34 sites
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Akashi-shi, 673-8558
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Akita, 010-8543
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Bunkyō City, 113-8431
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Chiba, 260-8717
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Chūōku, 104-0045
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Chūōku, 104-8560
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Fukuoka, 811-1395
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Fukushima, 960-1295
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Gifu, 501-1194
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Hidaka-shi, 350-1298
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Hirakata-shi, 573-1191
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Hiroshima, 730-0011
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Hiroshima, 734-8551
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Isehara-shi, 259-1193
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Kashiwa, 227-8577
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Kumamoto, 860-8556
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Kurume-shi, 830-0011
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Kyoto, 606-8507
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Matsuyama, 791-0280
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Nagoya, 460-0001
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Nagoya, 466-8560
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Nagoya, 467-0001
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Niigata, 951-8566
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Okayama, 700-8558
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Osaka, 541-8567
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Sapporo, 003-0804
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Sapporo, 060-8648
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Sendai, 980-8574
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Shinagawa-ku, 142-8666
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Shinjuku-ku, 160-0023
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Shinjuku-ku, 162-8655
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Sunto-gun, 411-8777
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Tsu, 514-8507
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Yokohama, 241-8515
China26 sites
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Beijing, 100044
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Bengbu, 233004
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Changchun, 130021
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Changsha, 410008
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Chengdu, 610000
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Guangzhou, 510060
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Guangzhou, 510120
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Hangzhou, 310009
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Hangzhou, 310022
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Harbin, 150049
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Jinan, 250117
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Linhai, 317000
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Nanchang, 330009
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Nanchang, 330029
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Nanjing, 210008
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Nanning, 530021
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Shanghai, 200025
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Shenyang, 110004
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Shijiazhuang, 050020
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Suining, 629000
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Tianjin, 300000
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Wuhan, 430022
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Xi'an, 710061
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Xintai, 54031
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Zhaoqing, 526000
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Zhengzhou, 450008
Germany20 sites
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Augsburg, 86150
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Berlin, 10967
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Berlin, 13125
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Dessau, 06847
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Dresden, 01307
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Erlangen, 91054
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Essen, 45130
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Esslingen am Neckar, 73730
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Frankfurt am Main, 60431
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Freiburg im Breisgau, 79110
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Hamburg, 20246
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Hanover, 30559
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Heidelberg, 69120
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Kiel, 24105
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Mainz, 55131
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Mannheim, 68167
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München, 80637
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Münster, 48149
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Trier, 54290
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Ulm, 89075
Canada14 sites
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Barrie, Ontario, L4M 6M2
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Calgary, Alberta, T2N 5G2
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Lévis, Quebec, G6V 3Z1
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London, Ontario, N6A 5W9
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Montreal, Quebec, H1T 2M4
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Montreal, Quebec, H2X 0C1
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Montreal, Quebec, H4A-3J1
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Montreal, H3T 1E2
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Oshawa, Ontario, L1G 2B9
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Ottawa, K1H 8L6
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Saint-Jérôme, Quebec, J7Z 5T3
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Sherbrooke, Quebec, J1H 5N4
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Toronto, Ontario, M5G 2M9
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Vancouver, British Columbia, VSZ 4E6
France13 sites
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Avignon, 84918
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Bayonne, 64100
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Caen, 41076
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Clermont-Ferrand, 63011
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Limoges, 87000
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Marseille, 13273
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Montpellier, 34298
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Nice, 06100
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Paris, 75010
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Reims, 51056
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Toulouse, 31100
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Vandœuvre-lès-Nancy, 54519
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Villejuif, 94805
Brazil12 sites
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Brasília, 71681-603
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Curitiba, 80440-220
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Fortaleza, 60336-045
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Londrina, 86015-520
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Natal, 59075-740
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Porto Alegre, 90035-000
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Porto Alegre, 90035-903
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Ribeirão Preto, 14051-140
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Santo André, 09060-650
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São Paulo, 01246-000
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Taubaté, 12030-200
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Vitória, 29043-260
Italy12 sites
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Empoli, 50053
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Lucca, 55100
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Milan, 20132
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Modena, 41124
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Naples, 80131
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Padova, 35128
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Province of Macerata, 62100
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Roma, 00168
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Rozzano, 20089
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Torino, 10126
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Tricase, 73039
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Udine, 33100
India10 sites
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Bengaluru, 560085
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Delhi, 110029
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Delhi, 110085
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Kolkata, 700016
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Kolkata, 700099
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Marg Jaipur, 302004
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Nagpur, 440001
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Nashik, 422011
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Thiruvananthapuram, 695011
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Vadodara, 391760
South Korea10 sites
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Daegu, 41404
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Goyang-si, 10408
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Seongnam, 13620
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Seoul, 02841
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Seoul, 03080
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Seoul, 03722
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Seoul, 05505
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Seoul, 06273
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Seoul, 06351
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Seoul, 06591
Spain8 sites
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Barcelona, 08036
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Granada, 18016
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Hospitalet deLlobregat, 08907
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Madrid, 28007
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Madrid, 28034
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Santiago de Compostela, 15706
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Seville, 41009
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Zaragoza, 50009
Taiwan8 sites
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Changhua, 500
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Kaohsiung City, 82445
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Taichung, 40447
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Tainan, 704
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Taipei, 10002
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Taipei, 10449
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Taipei, 112
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Taoyuan, 333
Turkey (Türkiye)7 sites
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Adapazarı, 54290
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Ankara, 06010
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Ankara, 06340
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Ankara, 06520
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Istanbul, 34722
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Kayseri, 38039
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Samsun, 55200
United Kingdom7 sites
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Birmingham, B15 2TG
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Cardiff, CF14 2TL
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Lancaster, LA1 4RP
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London, EC1A 7BE
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Northampton, NN1 5BD
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Oxford, OX3 7LE
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Taunton, TA1 5DA
Belgium6 sites
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Antwerp, 2020
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Brasschaat, 2930
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Charleroi, 6060
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Ghent, 9000
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Leuven, 3000
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Libramont-Chevigny, 6800
Poland6 sites
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Bialystok, 15-027
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Bydgoszcz, 85-796
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Gdynia, 81-519
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Krakow, 31-501
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Lodz, 93-338
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Warsaw, 02-781
Malaysia5 sites
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George Town, 10990
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Kuala Lumpur, 50586
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Kuala Lumpur, 59100
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Kuala Selangor, 62250
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Kuching, 93586
Thailand5 sites
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Bangkok, 10210
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Bangkok, 10330
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Dusit, 10300
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Muang, 50200
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Songkhla, 90110
Austria4 sites
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Feldkirch, 6807
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Innsbruck, 6020
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Linz, 4010
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Salzburg, 5020
Hungary4 sites
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Budapest, 1122
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Kecskemét, 6000
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Miskolc, 3526
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Szekszárd, 7100
Switzerland4 sites
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Baden, CH-5405
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Basel, 4031
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Bern, 3010
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Frauenfeld, 8501
Vietnam4 sites
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Hanoi, 100000
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Hồ Chí Minh, 700000
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Ho Chi Minh City, 700000
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Vinh, 460000
Bulgaria3 sites
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Shumen, 9700
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Sofia, 1330
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Sofia
About this study
Official title: 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)
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.
Read the detailed description
The primary objectives of the study are to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to 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, by investigator assessment of EFS.
- Conditions
- Breast Cancer
- Being tested
- Dato-DXd, Durvalumab, Pembrolizumab, Doxorubicin, Epirubicin
- Keywords
- Breast Cancer;, Dato-DXd; DS1062a;, TROP2;, TNBC;, HR low:, Datopotamab deruxtecan;, Antibody Drug Conjugate;, ADC;, neoadjuvant therapy;, adjuvant therapy;, durvalumab;, PD-L1;, immune-checkpoint inhibitor (ICI);
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dato-DXdDrug
Also called Datopotamab deruxtecan (Dato-DXd, DS-1062a)
Experimental drug IV infusion
DurvalumabDrug
Also called MEDI4736
Experimental drug IV Infusion
PembrolizumabDrug
Also called KEYTRUDA®
IV Infusion Active comparator
DoxorubicinDrug
IV infusion Experimental/Active Comparator
EpirubicinDrug
IV Infusion Experimental/Active Comparator
CyclophosphamideDrug
IV infusion Experimental/Active Comparator
PaclitaxelDrug
IV infusion Experimental/Active Comparator
CarboplatinDrug
IV infusion Experimental/Active Comparator
CapecitabineDrug
Also called XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine Accord
Tablet Oral route of administration Experimental/Active Comparator
OlaparibDrug
Also called LYNPARZA®
Tablet Oral route of administration Experimental/Active Comparator
| Study group | Role | What they receive |
|---|---|---|
| Dato-DXd plus durvalumab | Experimental | Participants 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. Receives: Drug: Dato-DXd; Drug: Durvalumab; Drug: Doxorubicin; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Carboplatin; Drug: Capecitabine; Drug: Olaparib |
| Pembrolizumab plus chemotherapy | Active comparator | Participants 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. Receives: Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Carboplatin; Drug: Capecitabine; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
pCR rate is defined as the proportion of participants who have no evidence by haematoxylin and eosin staining of residual invasive disease or lymphovascular invasion at the time of definitive surgery in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by blinded central evaluation.
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 difference between the pCR rates.
Measured: At the time of definitive surgery
Overall Survival (OS) in the experimental vs control arms
Key Secondary - OS is defined as the time from the date of randomisation until the date of death due to any cause.
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 OS.
Measured: 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
DDFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: distant metastasis, occurrence of second primary invasive cancer (other than squamous or basal cell skin cancer), relapse from prior malignancy or death by any cause (in the absence of recurrence). DDFS 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 DDFS.
Measured: 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
Breast and arm symptoms measured by the EORTC IL116. 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 is the mean between-arm difference in breast and arm symptom scores.
Measured: 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
Physical function measured by the PROMIS Physical Function Short Form 8c. The analysis will include all dosed participants. The measure of interest is the mean between-arm difference in physical function scores.
Measured: 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).
Participant-reported fatigue in the experimental vs. control arms
Fatigue measured by the PROMIS Fatigue Short Form 7a. The analysis will include all dosed participants. The measure of interest will be the difference on the proportions of participants reporting different levels of fatigue and mean between-arm difference in the fatigue scores.
Measured: 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).
Participant-reported Global health status/Quality of life (GHS/QoL)in the experimental vs. control arms
Global health status/Quality of life measured by EORTC IL172. 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 is the mean between-arm difference in GHS/QoL scores.
Measured: 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).
Pharmacokinetics of Dato-DXd (in combination with durvalumab)
Plasma concentrations of Dato-DXd (ug/ml )
Measured: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Pharmacokinetics of Dato-DXd (in combination with durvalumab)
Plasma concentrations of total anti-TROP2 antibody (ug/ml )
Measured: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Pharmacokinetics of Dato-DXd (in combination with durvalumab)
Plasma concentrations of DXd (MAAA-1181a) (ng/ml)
Measured: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Immunogenicity of Dato-DXd (in combination with durvalumab)
Presence of antidrug antibodies (ADAs) for Dato-DXd (confirmatory results: positive or negative, titres).
Measured: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Safety of Dato-DXd (in combination with durvalumab)
Safety and tolerability will be evaluated in terms of AEs graded by CTCAE version 5.0
Measured: Randomization to final safety follow-up visit, either 90 days after last dose of study intervention for those who complete planned study intervention or 90 days after date of discontinuation for those who discontinue study intervention prematurely
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2023
- Study start14 Nov 2023
- Primary completion20 Nov 2028 (estimated)
- Study completion23 Sep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomised in a 1:1 ratio to one of two intervention groups.
- Masking
- None (open label)
- Enrolment
- 1,902 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06112379
- Sponsor's protocol ID
- D926QC00001
- Other IDs
- 2023-505928-59-00, 2023
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2023
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
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.
PubMed 39917260
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06112379
- Acronym / sponsor ID
- D926QC00001
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer;, Dato-DXd; DS1062a;, TROP2;, TNBC;, HR low:, Datopotamab deruxtecan;, Antibody Drug Conjugate;, ADC;
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,902 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Study start
- 14 Nov 2023 (actual)
- Primary completion
- 20 Nov 2028 (estimated)
- Study completion
- 23 Sep 2032 (estimated)
- First posted
- 1 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary objectives of the study are to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to 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, by investigator assessment of EFS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be randomised in a 1:1 ratio to one of two intervention groups.
| Arm | Type | Receives |
|---|---|---|
| Dato-DXd plus durvalumab | Experimental | Drug: Dato-DXd, Drug: Durvalumab, Drug: Doxorubicin, Drug: Epirubicin, Drug: Cyclophosphamide, Drug: Paclitaxel, Drug: Carboplatin, Drug: Capecitabine, Drug: OlaparibParticipants 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 comparator | Drug: Pembrolizumab, Drug: Doxorubicin, Drug: Epirubicin, Drug: Cyclophosphamide, Drug: Paclitaxel, Drug: Carboplatin, Drug: Capecitabine, Drug: OlaparibParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dato-DXdAlso: Datopotamab deruxtecan (Dato-DXd, DS-1062a)Experimental drug IV infusion | Drug | Dato-DXd plus durvalumab |
| DurvalumabAlso: MEDI4736Experimental drug IV Infusion | Drug | Dato-DXd plus durvalumab |
| PembrolizumabAlso: KEYTRUDA®IV Infusion Active comparator | Drug | Pembrolizumab plus chemotherapy |
| DoxorubicinIV infusion Experimental/Active Comparator | Drug | Dato-DXd plus durvalumab, Pembrolizumab plus chemotherapy |
| EpirubicinIV Infusion Experimental/Active Comparator | Drug | Dato-DXd plus durvalumab, Pembrolizumab plus chemotherapy |
| CyclophosphamideIV infusion Experimental/Active Comparator | Drug | Dato-DXd plus durvalumab, Pembrolizumab plus chemotherapy |
| PaclitaxelIV infusion Experimental/Active Comparator | Drug | Dato-DXd plus durvalumab, Pembrolizumab plus chemotherapy |
| CarboplatinIV infusion Experimental/Active Comparator | Drug | Dato-DXd plus durvalumab, Pembrolizumab plus chemotherapy |
| CapecitabineAlso: XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine AccordTablet Oral route of administration Experimental/Active Comparator | Drug | Dato-DXd plus durvalumab, Pembrolizumab plus chemotherapy |
| OlaparibAlso: LYNPARZA®Tablet Oral route of administration Experimental/Active Comparator | Drug | Dato-DXd plus durvalumab, Pembrolizumab plus chemotherapy |
Primary outcome
Event-free survival (EFS) in the experimental vs control arms
Time frame: Date of randomization to date of the EFS event, up to 93 months after the first subject randomized
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.
12 secondary outcomes
Pathologic Complete Response (pCR) in the experimental vs control arms
Time frame: At the time of definitive surgery
Overall Survival (OS) in the experimental vs control arms
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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).
Participant-reported fatigue in the experimental vs. control arms
Time frame: 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).
Participant-reported Global health status/Quality of life (GHS/QoL)in the experimental vs. control arms
Time frame: 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).
Pharmacokinetics of Dato-DXd (in combination with durvalumab)
Time frame: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Pharmacokinetics of Dato-DXd (in combination with durvalumab)
Time frame: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Pharmacokinetics of Dato-DXd (in combination with durvalumab)
Time frame: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Immunogenicity of Dato-DXd (in combination with durvalumab)
Time frame: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Safety of Dato-DXd (in combination with durvalumab)
Time frame: Randomization to final safety follow-up visit, either 90 days after last dose of study intervention for those who complete planned study intervention or 90 days after date of discontinuation for those who discontinue study intervention prematurely
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Derived from this study: PubMed 39917260McArthur 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.
- Breast Cancer Study Locator details (for US)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
283 sites in 26 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dato-DXd, Durvalumab and Pembrolizumab in people with Breast Cancer, run by AstraZeneca at 283 sites in 26 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 283 sites in United States, Japan, China, Germany, Canada and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (EFS) in the experimental vs control arms (time frame: Date of randomization to date of the EFS event, up to 93 months after the first subject randomized). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06112379, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.