A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03)
A Phase 3 Open-label, Randomised Study of Datopotamab Deruxtecan (DatoDXd) With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Who Have Residual Invasive Disease in the Breast and/or Axillary Lymph Nodes at Surgical Resection Following Neoadjuvant Systemic Therapy (TROPION-Breast03)
3 other identifiers
interventional
1,174
17 countries
276
Brief Summary
This is a Phase III, randomized, open-label, 3-arm, multicenter, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with ICT in participants with stage I to III TNBC with residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy.
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 2022
Typical duration for phase_3 breast-cancer
276 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
November 4, 2022
CompletedStudy Start
First participant enrolled
November 28, 2022
CompletedFirst Posted
Study publicly available on registry
November 29, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 20, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 30, 2030
March 18, 2026
March 1, 2026
4.8 years
November 4, 2022
March 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Invasive disease-free survival (iDFS) for Dato-DXd + durvalumab vs. ICT
iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause. iDFS will be determined based on disease recurrence per investigator assessment 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 HR (hazard ratio) of iDFS for Dato-DXd + durvalumab vs ICT.
From randomisation to date of the event, up to 57 months from first subject in
Secondary Outcomes (13)
Distant disease-free survival (DDFS) for Dato-DXd + durvalumab vs ICT
From randomisation to date of the event, up to 57 months from first subject in
DDFS for Dato-DXd vs ICT
From randomisation to date of the event, up to 57 months from first subject in
DDFS for Dato-DXd + durvalumab vs Dato-DXd
From randomisation to date of the event, up 57 months from first subject in
Overall Survival (OS) for Dato-DXd + durvalumab vs ICT
From randomisation to date of death, due to any cause, up to 87 months from first subject in
OS for Dato-DXd vs ICT
From randomisation to date of death, due to any cause, up to 87 months from first subject in
- +8 more secondary outcomes
Study Arms (3)
Dato-DXd in combination with Durvalumab
EXPERIMENTALArm 1: Dato-DXd 6 mg/kg IV Q3W x 8 cycles + Durvalumab 1120 mg IV Q3W x 9 cycles
Dato-DXd
EXPERIMENTALArm 2: Dato-DXd 6 mg/kg IV Q3W x 8 cycles
Investigators Choice Therapy
ACTIVE COMPARATORArm 3: Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles Pembrolizumab\* (200 mg IV on Day 1, Q3W) for 9 cycles Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles + pembrolizumab\* (200 mg IV on Day 1, Q3W) for 9 cycles \* Only participants who have received prior pembrolizumab in the neoadjuvant setting should receive pembrolizumab as part of their adjuvant therapy on Arm 3.
Interventions
Experimental drug. Provided in 100mg vials. IV infusion
Experimental drug. Provided in 50mg vials. IV infusion
Active Comparator. Tablet. Oral route of administration
Active Comparator. Provided in 100mg vials. IV infusion
Eligibility Criteria
You may qualify if:
- Participant must be ≥ 18 years at the time of screening.
- Histologically confirmed invasive TNBC, as defined by the ASCO/CAP guidelines.
- Residual invasive disease in the breast and/or axillary lymph node(s) at surgical resection following neoadjuvant therapy.
- Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or a taxane with or without platinum chemotherapy, with or without pembrolizumab.
- No evidence of locoregional or distant relapse.
- Surgical removal of all clinically evident disease in the breast and lymph nodes.
- ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation.
- All participants must provide an FFPE tumour sample from residual invasive disease at surgery for tissue-based analysis.
- No adjuvant systemic therapy.
- Radiotherapy (if indicated) delivered before the start of study intervention.
- If post-operative radiation therapy is given, an interval of no more than 6 weeks between the completion of radiation therapy and the date of randomisation (radiation therapy can be completed during screening period). If no post-operative radiation therapy is given, an interval of no more than 16 weeks between the date of breast surgery and the date of randomisation.
- Has LVEF ≥ 50% by either an ECHO or MUGA scan within 28 days before randomisation.
- Eligible for one of the therapy options listed as investigator's choice per investigator assessment.
- No known germline BRCA1 or BRCA2 pathogenic mutation.
- Adequate bone marrow reserve and organ function within 7 days before randomisation.
You may not qualify if:
- Stage IV (metastatic) TNBC.
- History of prior invasive breast cancer, or evidence of recurrent disease following preoperative therapy and surgery.
- Severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, serious chronic gastrointestinal conditions associated with diarrhea chronic diverticulitis or previous complicated diverticulitis.
- History of another primary malignancy except for adequately resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin, in situ disease (including ductal carcinoma in situ) that has undergone potentially curative therapy, or other solid malignancy treated with curative intent with no known active disease within 5 years before randomisation and of low potential risk for recurrence.
- Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade ≤ 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).
- Active or prior documented autoimmune or inflammatory disorders.
- Clinically significant corneal disease.
- Active or uncontrolled hepatitis B or C virus infection.
- Known HIV infection that is not well controlled
- Active tuberculosis infection.
- Mean resting corrected QTcF \> 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening.
- Uncontrolled or significant cardiac disease.
- History of non-infectious ILD/pneumonitis including radiation, pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- Has severe pulmonary function compromise.
- Any known active liver disease.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyocollaborator
- SWOG Clinical Trials Partnershipscollaborator
Study Sites (276)
Research Site
Gilbert, Arizona, 85234, United States
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Tucson, Arizona, 85711, United States
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Tucson, Arizona, 85719, United States
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Hot Springs, Arkansas, 71913, United States
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Little Rock, Arkansas, 72205, United States
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Springdale, Arkansas, 72762, United States
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Beverly Hills, California, 90211, United States
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Costa Mesa, California, 92627, United States
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Duarte, California, 91010, United States
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Fountain Valley, California, 92708, United States
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Irvine, California, 92618, United States
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La Jolla, California, 92093, United States
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Lakewood, California, 90805, United States
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Los Angeles, California, 90017, United States
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Los Angeles, California, 90095, United States
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Newport Beach, California, 92660, United States
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Newport Beach, California, 92663, United States
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Orange, California, 92868, United States
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Roseville, California, 95661, United States
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Upland, California, 91786, United States
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Vallejo, California, 94589, United States
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Denver, Colorado, 80220, United States
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New Haven, Connecticut, 06510, United States
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Newark, Delaware, 19713, United States
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Washington D.C., District of Columbia, 20007, United States
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Altamonte Springs, Florida, 32701, United States
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Hollywood, Florida, 33021, United States
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Miami Beach, Florida, 33140, United States
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Tallahassee, Florida, 32308, United States
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West Palm Beach, Florida, 33401, United States
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Athens, Georgia, 30607, United States
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Atlanta, Georgia, 30318, United States
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Atlanta, Georgia, 30322, United States
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Chicago, Illinois, 60611, United States
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Maywood, Illinois, 60153, United States
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Westwood, Kansas, 66205, United States
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Lexington, Kentucky, 40503, United States
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Louisville, Kentucky, 40202, United States
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Louisville, Kentucky, 40207, United States
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Louisville, Kentucky, 40241, United States
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New Orleans, Louisiana, 70121, United States
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Annapolis, Maryland, 21401, United States
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Baltimore, Maryland, 21202, United States
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Columbia, Maryland, 21044, United States
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Boston, Massachusetts, 02114, United States
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Detroit, Michigan, 48201, United States
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St Louis, Missouri, 63110, United States
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Camden, New Jersey, 08103, United States
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Albuquerque, New Mexico, 87109, United States
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New York, New York, 10011, United States
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New York, New York, 10021, United States
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New York, New York, 10029, United States
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New York, New York, 10032, 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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Canton, Ohio, 44710, United States
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Cleveland, Ohio, 44106, United States
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Cleveland, Ohio, 44111, United States
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Cleveland, Ohio, 44195, United States
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Columbus, Ohio, 43219, United States
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Portland, Oregon, 97227, United States
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Hershey, Pennsylvania, 17033, United States
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Philadelphia, Pennsylvania, 19111, United States
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Pittsburgh, Pennsylvania, 15213, United States
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Providence, Rhode Island, 02903, United States
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Germantown, Tennessee, 38138, United States
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Memphis, Tennessee, 38120, United States
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Nashville, Tennessee, 37203, United States
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Nashville, Tennessee, 37232, United States
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Bedford, Texas, 76022, United States
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Dallas, Texas, 75246, United States
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Denton, Texas, 76201, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77024, United States
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Houston, Texas, 77030, United States
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McAllen, Texas, 78503, United States
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Tyler, Texas, 75702, United States
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Fairfax, Virginia, 22031, United States
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Gainesville, Virginia, 20155, United States
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Midlothian, Virginia, 23114, United States
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Norfolk, Virginia, 23502, United States
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Edmonds, Washington, 98026, United States
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Issaquah, Washington, 98029, United States
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Puyallup, Washington, 98373, United States
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Seattle, Washington, 98104, United States
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Seattle, Washington, 98133, United States
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Spokane Valley, Washington, 99216, United States
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Morgantown, West Virginia, 26506, United States
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Anderlecht, 1070, Belgium
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Brussels, 1090, Belgium
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Brussels, 1200, Belgium
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Charleroi, 6060, Belgium
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Edegem, 2650, Belgium
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Ghent, 9000, Belgium
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Hasselt, 3500, Belgium
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Liège, 4000, Belgium
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Namur, 5000, Belgium
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Sint-Niklaas, 9100, Belgium
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Wilrijk, 2610, Belgium
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Brasília, 71681-603, Brazil
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Porto Alegre, 90035-000, Brazil
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Recife, 52010-075, Brazil
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Salvador, 41253-190, Brazil
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São Paulo, 01321-001, Brazil
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São Paulo, 01508-010, Brazil
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São Paulo, 03102-002, Brazil
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São Paulo, 04532-030, Brazil
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Vitória, 29055-450, Brazil
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North Vancouver, British Columbia, V7L 2L7, Canada
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Barrie, Ontario, L4M 6M2, Canada
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Kingston, Ontario, K7L 2V7, Canada
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Oakville, Ontario, L9T 6G2, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M5G 1X5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Laval, Quebec, H7M 3L9, Canada
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Montreal, Quebec, H2X 0C1, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Québec, Quebec, G1S 4L8, Canada
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Saskatoon, Saskatchewan, S7N 4H4, Canada
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Beijing, 100044, China
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Beijing, 100142, 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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Chengdu, 610072, China
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Chongqing, 400030, China
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Fuzhou, 350011, China
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Guangzhou, 510060, China
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Guangzhou, 510100, China
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Guangzhou, 510120, China
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Guangzhou, 510700, China
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Haikou, 570311, China
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Hangzhou, 310009, China
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Hangzhou, 310020, China
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Harbin, 150081, China
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Hefei, 230001, China
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Jinan, 250030, China
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Nanchang, 330009, China
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Nanjing, 210008, China
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Nanjing, 210009, China
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Nanning, 530021, China
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Qingdao, 110016, China
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Shanghai, 200025, China
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Shanghai, 200032, China
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Shenzhen, 518020, China
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Shijiazhuang, 050020, China
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Tianjin, 300060, China
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Wuhan, 430022, China
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Wuhan, 430060, China
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Xi'an, 710038, China
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Xiamen, 361003, China
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Zhengzhou, 450052, China
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Copenhagen, 2100, Denmark
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Herning, 7400, Denmark
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Næstved, 4700, Denmark
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Odense, 5000, Denmark
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Sønderborg, 6400, Denmark
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Vejle, 7100, Denmark
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Angers, 49055, France
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Bordeaux, 33076, France
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Dijon, 21000, France
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Lyon, 69008, France
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Montpellier, 34070, France
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Nîmes, 30029, France
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Paris, 75248, France
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Poitiers, 86021, France
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Rennes, 35000, France
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Saint-Herblain, 44805, France
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Villejuif, 94805, France
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Frankfurt am Main, 65929, Germany
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Hamburg, 20357, Germany
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Hanover, 30177, Germany
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Heilbronn, 74078, Germany
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Kiel, 24105, Germany
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Langen, 63225, Germany
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Leipzig, 4103, Germany
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Ludwigsburg, 71640, Germany
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Mönchengladbach, 41061, Germany
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München, 80337, Germany
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Paderborn, 33098, Germany
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Regensburg, 93053, Germany
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Stuttgart, 70199, Germany
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Troisdorf, 53840, Germany
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Tübingen, 72076, Germany
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Wuppertal, 42283, Germany
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Athens, 115 22, Greece
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Athens, 11528, Greece
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Athens, 12462, Greece
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Heraklion, 71110, Greece
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Thessaloniki, 54639, Greece
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Thessaloniki, 57001, Greece
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Bologna, 40138, Italy
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Brescia, 25123, Italy
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Florence, 50134, Italy
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Genova, 16132, Italy
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Livorno, 57124, Italy
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Meldola, 47014, Italy
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Messina, 98158, Italy
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Milan, 20132, Italy
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Milan, 20141, 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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Akashi-shi, 673-8558, Japan
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Chiba, 260-8717, Japan
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Chūōku, 104-0045, Japan
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Fukuoka, 811-1395, Japan
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Fukushima, 960-1295, Japan
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Hiroshima, 730-8518, Japan
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Isehara-shi, 259-1193, Japan
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Kashiwa, 277-8577, Japan
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Kōtoku, 135-8550, Japan
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Kyoto, 606-8507, Japan
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Matsuyama, 791-0280, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 466-8560, Japan
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Niigata, 951-8566, Japan
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Nishinomiya-shi, 663-8501, Japan
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Okayama, 700-8558, Japan
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Osaka, 541-8567, Japan
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Ota-shi, 373-8550, Japan
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Sapporo, 003-0804, Japan
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Sendai, 980-8574, Japan
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Shinagawa-ku, 142-8666, Japan
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Shinjuku-ku, 162-8655, Japan
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Tsukuba, 305-8577, Japan
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Yokohama, 241-8515, Japan
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San Juan, 00918, Puerto Rico
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Busan, 49241, South Korea
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Daegu, 41404, South Korea
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Goyang-si, 10408, South Korea
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Seongnam-si, 463-712, 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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Barcelona, 08028, Spain
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Barcelona, 8035, Spain
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Bilbao (Vizcaya), 48013, Spain
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Elche(Alicante), 03202, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Málaga, 29010, Spain
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Palma de Mallorca, 07010, Spain
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Toledo, 45007, Spain
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Valencia, 46010, Spain
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Stockholm, 11281, Sweden
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Stockholm, 17176, Sweden
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Sundsvall, 851 86, Sweden
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Uppsala, 751 85, Sweden
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Hsinchu, 300, Taiwan
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Taichung, 40447, Taiwan
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Tainan, 70403, 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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Yung Kang City, 71044, Taiwan
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Cambridge, CB2 0QQ, United Kingdom
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Cardiff, CF14 2TL, United Kingdom
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Edinburgh, EH4 2XU, United Kingdom
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Greater London, SW3 6JJ, United Kingdom
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London, EC1A 7BE, United Kingdom
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London, SE1 9RT, United Kingdom
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Londonderry, BT47 6SB, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Newcastle upon Tyne, NE7 7AF, United Kingdom
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Portsmouth, PO6 3LY, United Kingdom
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Surrey, SM2 5PT, United Kingdom
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Taunton, TA1 5DA, United Kingdom
Related Publications (1)
Bardia A, Pusztai L, Albain K, Ciruelos EM, Im SA, Hershman D, Kalinsky K, Isaacs C, Loirat D, Testa L, Tokunaga E, Wu J, Dry H, Barlow W, Kozarski R, Maxwell M, Harbeck N, Sharma P. TROPION-Breast03: a randomized phase III global trial of datopotamab deruxtecan +/- durvalumab in patients with triple-negative breast cancer and residual invasive disease at surgical resection after neoadjuvant therapy. Ther Adv Med Oncol. 2024 Apr 29;16:17588359241248336. doi: 10.1177/17588359241248336. eCollection 2024.
PMID: 38686016DERIVED
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
November 4, 2022
First Posted
November 29, 2022
Study Start
November 28, 2022
Primary Completion (Estimated)
September 20, 2027
Study Completion (Estimated)
January 30, 2030
Last Updated
March 18, 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 de-identified 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 requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.