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)
Dato-DXd: Experimental drug. Provided in 100mg vials. IV infusion
Durvalumab: Experimental drug. Provided in 50mg vials. IV infusion
Capecitabine: Active Comparator. Tablet. Oral route of administration
Pembrolizumab: Active Comparator. Provided in 100mg vials. IV infusion
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
130 Years
Healthy volunteers
No
Inclusion Criteria:
1. Participant must be ≥ 18 years at the time of screening.
2. Histologically confirmed invasive TNBC, as defined by the ASCO/CAP guidelines.
3. Residual invasive disease in the breast and/or axillary lymph node(s) at surgical resection following neoadjuvant therapy.
4. Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or a taxane with or without platinum chemotherapy, with or without pembrolizumab.
5. No evidence of locoregional or distant relapse.
6. Surgical removal of all clinically evident disease in the breast and lymph nodes.
7. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation.
8. All participants must provide an FFPE tumour sample from residual invasive disease at surgery for tissue-based analysis.
9. No adjuvant systemic therapy.
10. Radiotherapy (if indicated) delivered before the start of study intervention.
11. 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.
12. Has LVEF ≥ 50% by either an ECHO or MUGA scan within 28 days before randomisation.
13. Eligible for one of the therapy options listed as investigator's choice per investigator assessment.
14. No known germline BRCA1 or BRCA2 pathogenic mutation.
15. Adequate bone marrow reserve and organ function within 7 days before randomisation.
Exclusion Criteria:
1. Stage IV (metastatic) TNBC.
2. History of prior invasive breast cancer, or evidence of recurrent disease following preoperative therapy and surgery.
3. 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.
4. 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.
5. 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).
6. Active or prior documented autoimmune or inflammatory disorders.
7. Clinically significant corneal disease.
8. Active or uncontrolled hepatitis B or C virus infection.
9. Known HIV infection that is not well controlled
10. Active tuberculosis infection.
11. Mean resting corrected QTcF \> 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening.
12. Uncontrolled or significant cardiac disease.
13. 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.
14. Has severe pulmonary function compromise.
15. Any known active liver disease.
16. Grade ≥ 2 peripheral neuropathy of any aetiology.
17. Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab.
18. Current or prior use of immunosuppressive medication within 14 days prior to randomisation.
19. Participants with a known severe hypersensitivity to Dato-DXd or any of the excipients of these products including but not limited to polysorbate 80 or other monoclonal antibodies.
20. Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors.
21. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to randomisation, randomisation into a prior Dato-DXd, T-DXd, or durvalumab study regardless of treatment assignment.
22. Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.
Primary outcome measure(s)
Invasive disease-free survival (iDFS) for Dato-DXd + durvalumab vs. ICT — From randomisation to date of the event, up to 57 months from first subject in 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.
Trial sites (276)
Facility
City
Region
Status
Research Site
Gilbert
Arizona
Research Site
Tucson
Arizona
Research Site
Tucson
Arizona
Research Site
Hot Springs
Arkansas
Research Site
Little Rock
Arkansas
Research Site
Springdale
Arkansas
Research Site
Beverly Hills
California
Research Site
Costa Mesa
California
Research Site
Duarte
California
Research Site
Fountain Valley
California
Research Site
Irvine
California
Research Site
La Jolla
California
Research Site
Lakewood
California
Research Site
Los Angeles
California
Research Site
Los Angeles
California
Research Site
Newport Beach
California
Research Site
Newport Beach
California
Research Site
Orange
California
Research Site
Roseville
California
Research Site
Upland
California
Research Site
Vallejo
California
Research Site
Denver
Colorado
Research Site
New Haven
Connecticut
Research Site
Newark
Delaware
Research Site
Washington D.C.
District of Columbia
Research Site
Altamonte Springs
Florida
Research Site
Hollywood
Florida
Research Site
Miami Beach
Florida
Research Site
Tallahassee
Florida
Research Site
West Palm Beach
Florida
Research Site
Athens
Georgia
Research Site
Atlanta
Georgia
Research Site
Atlanta
Georgia
Research Site
Chicago
Illinois
Research Site
Maywood
Illinois
Research Site
Westwood
Kansas
Research Site
Lexington
Kentucky
Research Site
Louisville
Kentucky
Research Site
Louisville
Kentucky
Research Site
Louisville
Kentucky
+ 236 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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