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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Dato-DXd; Drug: Durvalumab; Drug: Doxorubicin; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Carboplatin; Drug: Capecitabine; Drug: Olaparib; Drug: Pembrolizumab

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 Type: Interventional
• Enrollment (Actual): 1902
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • East Melbourne, Australia, 3002
    • Research Site
• Austria
  • Feldkirch, Austria, 6807
    • Research Site
  • Innsbruck, Austria, 6020
    • Research Site
  • Linz, Austria, 4010
    • Research Site
  • Salzburg, Austria, 5020
    • Research Site
• Belgium
  • Antwerp, Belgium, 2020
    • Research Site
  • Brasschaat, Belgium, 2930
    • Research Site
  • Charleroi, Belgium, 6060
    • Research Site
  • Ghent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Libramont-Chevigny, Belgium, 6800
    • Research Site
• Brazil
  • Brasília, Brazil, 71681-603
    • Research Site
  • Curitiba, Brazil, 80440-220
    • Research Site
  • Fortaleza, Brazil, 60336-045
    • Research Site
  • Londrina, Brazil, 86015-520
    • Research Site
  • Natal, Brazil, 59075-740
    • Research Site
  • Porto Alegre, Brazil, 90035-903
    • Research Site
  • Porto Alegre, Brazil, 90035-000
    • Research Site
  • Ribeirão Preto, Brazil, 14051-140
    • Research Site
  • Santo André, Brazil, 09060-650
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Research Site
  • Taubaté, Brazil, 12030-200
    • Research Site
  • Vitória, Brazil, 29043-260
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• Bulgaria
  • Shumen, Bulgaria, 9700
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Sofia, Bulgaria, 1330
    • Research Site
• Canada
  • Montreal, Canada, H3T 1E2
    • Research Site
  • Ottawa, Canada, K1H 8L6
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, VSZ 4E6
      • Research Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Research Site
    • London, Ontario, Canada, N6A 5W9
      • Research Site
    • Oshawa, Ontario, Canada, L1G 2B9
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Quebec
    • Lévis, Quebec, Canada, G6V 3Z1
      • Research Site
    • Montreal, Quebec, Canada, H2X 0C1
      • Research Site
    • Montreal, Quebec, Canada, H1T 2M4
      • Research Site
    • Montreal, Quebec, Canada, H4A-3J1
      • Research Site
    • Saint-Jérôme, Quebec, Canada, J7Z 5T3
      • Research Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
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• China
  • Beijing, China, 100044
    • Research Site
  • Bengbu, China, 233004
    • Research Site
  • Changchun, China, 130021
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  • Changsha, China, 410008
    • Research Site
  • Chengdu, China, 610000
    • Research Site
  • Guangzhou, China, 510120
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  • Guangzhou, China, 510060
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  • Hangzhou, China, 310022
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  • Hangzhou, China, 310009
    • Research Site
  • Harbin, China, 150049
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  • Jinan, China, 250117
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  • Linhai, China, 317000
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  • Nanchang, China, 330009
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  • Nanchang, China, 330029
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  • Nanjing, China, 210008
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  • Nanning, China, 530021
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  • Shanghai, China, 200025
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  • Shenyang, China, 110004
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  • Shijiazhuang, China, 050020
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  • Suining, China, 629000
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  • Tianjin, China, 300000
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  • Wuhan, China, 430022
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  • Xi'an, China, 710061
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  • Xintai, China, 54031
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  • Zhaoqing, China, 526000
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  • Zhengzhou, China, 450008
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• France
  • Avignon, France, 84918
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  • Bayonne, France, 64100
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  • Caen, France, 41076
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  • Clermont-Ferrand, France, 63011
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  • Limoges, France, 87000
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  • Marseille, France, 13273
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  • Montpellier, France, 34298
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  • Nice, France, 06100
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  • Paris, France, 75010
    • Research Site
  • Reims, France, 51056
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  • Toulouse, France, 31100
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  • Vandœuvre-lès-Nancy, France, 54519
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Germany
  • Augsburg, Germany, 86150
    • Research Site
  • Berlin, Germany, 13125
    • Research Site
  • Berlin, Germany, 10967
    • Research Site
  • Dessau, Germany, 06847
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  • Dresden, Germany, 01307
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  • Erlangen, Germany, 91054
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  • Essen, Germany, 45130
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  • Esslingen am Neckar, Germany, 73730
    • Research Site
  • Frankfurt am Main, Germany, 60431
    • Research Site
  • Freiburg im Breisgau, Germany, 79110
    • Research Site
  • Hamburg, Germany, 20246
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  • Hanover, Germany, 30559
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  • Heidelberg, Germany, 69120
    • Research Site
  • Kiel, Germany, 24105
    • Research Site
  • Mainz, Germany, 55131
    • Research Site
  • Mannheim, Germany, 68167
    • Research Site
  • München, Germany, 80637
    • Research Site
  • Münster, Germany, 48149
    • Research Site
  • Trier, Germany, 54290
    • Research Site
  • Ulm, Germany, 89075
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Research Site
• Hungary
  • Budapest, Hungary, 1122
    • Research Site
  • Kecskemét, Hungary, 6000
    • Research Site
  • Miskolc, Hungary, 3526
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  • Szekszárd, Hungary, 7100
    • Research Site
• India
  • Bengaluru, India, 560085
    • Research Site
  • Delhi, India, 110085
    • Research Site
  • Delhi, India, 110029
    • Research Site
  • Kolkata, India, 700099
    • Research Site
  • Kolkata, India, 700016
    • Research Site
  • Marg Jaipur, India, 302004
    • Research Site
  • Nagpur, India, 440001
    • Research Site
  • Nashik, India, 422011
    • Research Site
  • Thiruvananthapuram, India, 695011
    • Research Site
  • Vadodara, India, 391760
    • Research Site
• Italy
  • Empoli, Italy, 50053
    • Research Site
  • Lucca, Italy, 55100
    • Research Site
  • Macerata, Italy, 62100
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Modena, Italy, 41124
    • Research Site
  • Naples, Italy, 80131
    • Research Site
  • Padova, Italy, 35128
    • Research Site
  • Roma, Italy, 00168
    • Research Site
  • Rozzano, Italy, 20089
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  • Torino, Italy, 10126
    • Research Site
  • Tricase, Italy, 73039
    • Research Site
  • Udine, Italy, 33100
    • Research Site
• Japan
  • Akashi-shi, Japan, 673-8558
    • Research Site
  • Akita, Japan, 010-8543
    • Research Site
  • Bunkyō City, Japan, 113-8431
    • Research Site
  • Chiba, Japan, 260-8717
    • Research Site
  • Chūōku, Japan, 104-0045
    • Research Site
  • Chūōku, Japan, 104-8560
    • Research Site
  • Fukuoka, Japan, 811-1395
    • Research Site
  • Fukushima, Japan, 960-1295
    • Research Site
  • Gifu, Japan, 501-1194
    • Research Site
  • Hidaka-shi, Japan, 350-1298
    • Research Site
  • Hirakata-shi, Japan, 573-1191
    • Research Site
  • Hiroshima, Japan, 734-8551
    • Research Site
  • Hiroshima, Japan, 730-0011
    • Research Site
  • Isehara-shi, Japan, 259-1193
    • Research Site
  • Kashiwa, Japan, 227-8577
    • Research Site
  • Kumamoto, Japan, 860-8556
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Research Site
  • Kyoto, Japan, 606-8507
    • Research Site
  • Matsuyama, Japan, 791-0280
    • Research Site
  • Nagoya, Japan, 466-8560
    • Research Site
  • Nagoya, Japan, 460-0001
    • Research Site
  • Nagoya, Japan, 467-0001
    • Research Site
  • Niigata, Japan, 951-8566
    • Research Site
  • Okayama, Japan, 700-8558
    • Research Site
  • Osaka, Japan, 541-8567
    • Research Site
  • Sapporo, Japan, 060-8648
    • Research Site
  • Sapporo, Japan, 003-0804
    • Research Site
  • Sendai, Japan, 980-8574
    • Research Site
  • Shinagawa-ku, Japan, 142-8666
    • Research Site
  • Shinjuku-ku, Japan, 162-8655
    • Research Site
  • Shinjuku-ku, Japan, 160-0023
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Research Site
  • Tsu, Japan, 514-8507
    • Research Site
  • Yokohama, Japan, 241-8515
    • Research Site
• Malaysia
  • George Town, Malaysia, 10990
    • Research Site
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Kuala Lumpur, Malaysia, 50586
    • Research Site
  • Kuala Selangor, Malaysia, 62250
    • Research Site
  • Kuching, Malaysia, 93586
    • Research Site
• Poland
  • Bialystok, Poland, 15-027
    • Research Site
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Gdynia, Poland, 81-519
    • Research Site
  • Krakow, Poland, 31-501
    • Research Site
  • Lodz, Poland, 93-338
    • Research Site
  • Warsaw, Poland, 02-781
    • Research Site
• Singapore
  • Singapore, Singapore, 168583
    • Research Site
• South Korea
  • Daegu, South Korea, 41404
    • Research Site
  • Goyang-si, South Korea, 10408
    • Research Site
  • Seongnam, South Korea, 13620
    • Research Site
  • Seoul, South Korea, 02841
    • 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
  • Seoul, South Korea, 06591
    • Research Site
• Spain
  • Barcelona, Spain, 08036
    • Research Site
  • Granada, Spain, 18016
    • Research Site
  • Hospitalet deLlobregat, Spain, 08907
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Santiago de Compostela, Spain, 15706
    • Research Site
  • Seville, Spain, 41009
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Switzerland
  • Baden, Switzerland, CH-5405
    • Research Site
  • Basel, Switzerland, 4031
    • Research Site
  • Bern, Switzerland, 3010
    • Research Site
  • Frauenfeld, Switzerland, 8501
    • Research Site
• Taiwan
  • Changhua, Taiwan, 500
    • Research Site
  • Kaohsiung City, Taiwan, 82445
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Tainan, Taiwan, 704
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 10449
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
  • Taoyuan District, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10210
    • Research Site
  • Bangkok, Thailand, 10330
    • Research Site
  • Dusit, Thailand, 10300
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
  • Songkhla, Thailand, 90110
    • Research Site
• Turkey (Türkiye)
  • Adapazarı, Turkey (Türkiye), 54290
    • Research Site
  • Ankara, Turkey (Türkiye), 06520
    • Research Site
  • Ankara, Turkey (Türkiye), 06010
    • Research Site
  • Ankara, Turkey (Türkiye), 06340
    • Research Site
  • Istanbul, Turkey (Türkiye), 34722
    • Research Site
  • Kayseri, Turkey (Türkiye), 38039
    • Research Site
  • Samsun, Turkey (Türkiye), 55200
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TG
    • Research Site
  • Cardiff, United Kingdom, CF14 2TL
    • Research Site
  • Lancaster, United Kingdom, LA1 4RP
    • Research Site
  • London, United Kingdom, EC1A 7BE
    • Research Site
  • Northampton, United Kingdom, NN1 5BD
    • Research Site
  • Oxford, United Kingdom, OX3 7LE
    • Research Site
  • Taunton, United Kingdom, TA1 5DA
    • Research Site
• United States
  • Alabama
    • Daphne, Alabama, United States, 36526
      • Research Site
  • Arizona
    • Prescott, Arizona, United States, 86301
      • Research Site
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Research Site
    • Rogers, Arkansas, United States, 72758
      • Research Site
  • California
    • Los Angeles, California, United States, 90033
      • Research Site
    • Santa Barbara, California, United States, 93105
      • Research Site
    • Santa Rosa, California, United States, 92805
      • Research Site
    • Torrance, California, United States, 90505
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
    • Longmont, Colorado, United States, 80504
      • Research Site
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Research Site
    • New Haven, Connecticut, United States, 06510
      • Research Site
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Research Site
    • Jacksonville, Florida, United States, 32256
      • Research Site
    • St. Petersburg, Florida, United States, 33705
      • Research Site
    • West Palm Beach, Florida, United States, 33401
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Research Site
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Research Site
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Research Site
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70817
      • Research Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Research Site
    • Traverse City, Michigan, United States, 49684
      • Research Site
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Research Site
    • Minneapolis, Minnesota, United States, 55407
      • Research Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Research Site
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Research Site
    • New Brunswick, New Jersey, United States, 08901
      • Research Site
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Durham, North Carolina, United States, 27710
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • Ohio
    • Blue Ash, Ohio, United States, 45242
      • Research Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Research Site
    • Portland, Oregon, United States, 97223
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Austin, Texas, United States, 78731
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • Dallas, Texas, United States, 75235
      • Research Site
    • Dallas, Texas, United States, 75390-8843
      • Research Site
    • El Paso, Texas, United States, 79902
      • Research Site
    • Flower Mound, Texas, United States, 75028
      • Research Site
    • Fort Worth, Texas, United States, 76104
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78240
      • Research Site
    • Webster, Texas, United States, 77598
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site
    • Norfolk, Virginia, United States, 23502
      • Research Site
    • Roanoke, Virginia, United States, 24014
      • Research Site
    • Winchester, Virginia, United States, 22601
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site
  • Hồ Chí Minh, Vietnam, 700000
    • Research Site
  • Vinh, Vietnam, 460000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion criteria:

• 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.
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dato-DXd plus durvalumab; 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: 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);; Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) for 4 cycles (12 weeks);; Carboplatin (weekly or Q3W) + paclitaxel (weekly) for 4 cycles (12 weeks);; Capecitabine (Q3W) for 8 cycles.	Drug: Dato-DXd; Experimental drug IV infusion; Other Names: Datopotamab deruxtecan (Dato-DXd, DS-1062a); Drug: Durvalumab; Experimental drug IV Infusion; Other Names: MEDI4736; Drug: Doxorubicin; IV infusion Experimental/Active Comparator; Drug: Epirubicin; IV Infusion Experimental/Active Comparator; Drug: Cyclophosphamide; IV infusion Experimental/Active Comparator; Drug: Paclitaxel; IV infusion Experimental/Active Comparator; Drug: Carboplatin; IV infusion Experimental/Active Comparator; Drug: Capecitabine; Tablet Oral route of administration Experimental/Active Comparator; Other Names: XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine Accord; Drug: Olaparib; Tablet Oral route of administration Experimental/Active Comparator; Other Names: LYNPARZA®
Active Comparator: Pembrolizumab plus chemotherapy; 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.	Drug: Doxorubicin; IV infusion Experimental/Active Comparator; Drug: Epirubicin; IV Infusion Experimental/Active Comparator; Drug: Cyclophosphamide; IV infusion Experimental/Active Comparator; Drug: Paclitaxel; IV infusion Experimental/Active Comparator; Drug: Carboplatin; IV infusion Experimental/Active Comparator; Drug: Capecitabine; Tablet Oral route of administration Experimental/Active Comparator; Other Names: XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine Accord; Drug: Olaparib; Tablet Oral route of administration Experimental/Active Comparator; Other Names: LYNPARZA®; Drug: Pembrolizumab; IV Infusion Active comparator; Other Names: KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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 )	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 )	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)	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).	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	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
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.	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.	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.	Date of randomization to date of the DDFS event, up to 93 months after the first subject randomized

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo

Publications and helpful links

General 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.

Helpful Links

• Breast Cancer Study Locator details (for US)

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2023
• Primary Completion (Estimated): November 20, 2028
• Study Completion (Estimated): September 23, 2032

Study Registration Dates

• First Submitted: October 12, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer;; Dato-DXd; DS1062a;; TROP2;; Datopotamab deruxtecan;; Antibody Drug Conjugate;; TNBC;; HR low:; ADC;; neoadjuvant therapy;; adjuvant therapy;; durvalumab;; PD-L1;; immune-checkpoint inhibitor (ICI)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nucleosides; Uracil; Pyrimidinones; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Deoxyribonucleosides; Fluorouracil; Capecitabine; Cyclophosphamide; Carboplatin; Doxorubicin; Paclitaxel; Epirubicin; pembrolizumab; durvalumab; olaparib
• Other Study ID Numbers: D926QC00001; 2023-505928-59-00 (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-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
• 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 rerefer 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 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.
• 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