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)
- Conditions
- Breast Cancer
- Registration Number
- NCT05629585
- Lead Sponsor
- AstraZeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 1075
Inclusion Criteria:<br><br> 1. Participant must be = 18 years at the time of screening.<br><br> 2. Histologically confirmed invasive TNBC, as defined by the ASCO/CAP guidelines.<br><br> 3. Residual invasive disease in the breast and/or axillary lymph node(s) at surgical<br> resection following neoadjuvant therapy.<br><br> 4. Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline<br> and/or a taxane with or without platinum chemotherapy, with or without<br> pembrolizumab.<br><br> 5. No evidence of locoregional or distant relapse.<br><br> 6. Surgical removal of all clinically evident disease in the breast and lymph nodes.<br><br> 7. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks<br> prior to randomisation.<br><br> 8. All participants must provide an FFPE tumour sample from residual invasive disease<br> at surgery for tissue-based analysis.<br><br> 9. No adjuvant systemic therapy.<br><br> 10. Radiotherapy (if indicated) delivered before the start of study intervention.<br><br> 11. If post-operative radiation therapy is given, an interval of no more than 6 weeks<br> between the completion of radiation therapy and the date of randomisation (radiation<br> therapy can be completed during screening period). If no post-operative radiation<br> therapy is given, an interval of no more than 16 weeks between the date of breast<br> surgery and the date of randomisation.<br><br> 12. Has LVEF = 50% by either an ECHO or MUGA scan within 28 days before randomisation.<br><br> 13. Eligible for one of the therapy options listed as investigator's choice per<br> investigator assessment.<br><br> 14. No known germline BRCA1 or BRCA2 pathogenic mutation.<br><br> 15. Adequate bone marrow reserve and organ function within 7 days before randomisation.<br><br>Exclusion Criteria:<br><br> 1. Stage IV (metastatic) TNBC.<br><br> 2. History of prior invasive breast cancer, or evidence of recurrent disease following<br> preoperative therapy and surgery.<br><br> 3. Severe or uncontrolled medical conditions including systemic diseases, history of<br> allogeneic organ transplant and active bleeding diseases, ongoing or active<br> infection, serious chronic gastrointestinal conditions associated with diarrhea<br> chronic diverticulitis or previous complicated diverticulitis.<br><br> 4. History of another primary malignancy except for adequately resected basal cell<br> carcinoma of the skin or squamous cell carcinoma of the skin, in situ disease<br> (including ductal carcinoma in situ) that has undergone potentially curative<br> therapy, or other solid malignancy treated with curative intent with no known active<br> disease within 5 years before randomisation and of low potential risk for<br> recurrence.<br><br> 5. Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not<br> yet improved to Grade = 1 or baseline. Participants with irreversible toxicity that<br> is not reasonably expected to be exacerbated by study intervention may be included<br> (eg, hearing loss).<br><br> 6. Active or prior documented autoimmune or inflammatory disorders.<br><br> 7. Clinically significant corneal disease.<br><br> 8. Active or uncontrolled hepatitis B or C virus infection.<br><br> 9. Known HIV infection that is not well controlled<br><br> 10. Active tuberculosis infection.<br><br> 11. Mean resting corrected QTcF > 470 ms regardless of gender, obtained from triplicate<br> 12-lead ECGs performed at screening.<br><br> 12. Uncontrolled or significant cardiac disease.<br><br> 13. History of non-infectious ILD/pneumonitis including radiation, pneumonitis that<br> required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis<br> that cannot be ruled out by imaging at screening.<br><br> 14. Has severe pulmonary function compromise.<br><br> 15. Any known active liver disease.<br><br> 16. Grade = 2 peripheral neuropathy of any aetiology.<br><br> 17. Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab.<br><br> 18. Current or prior use of immunosuppressive medication within 14 days prior to<br> randomisation.<br><br> 19. Participants with a known severe hypersensitivity to Dato-DXd or any of the<br> excipients of these products including but not limited to polysorbate 80 or other<br> monoclonal antibodies.<br><br> 20. Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors.<br><br> 21. Participation in another clinical study with a study intervention or investigational<br> medicinal device administered in the last 4 weeks prior to randomisation,<br> randomisation into a prior Dato-DXd, T-DXd, or durvalumab study regardless of<br> treatment assignment.<br><br> 22. Currently pregnant (confirmed with positive pregnancy test), breastfeeding or<br> planning to become pregnant.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Invasive disease-free survival (iDFS) for Dato-DXd + durvalumab vs. ICT
- Secondary Outcome Measures
Name Time Method Distant disease-free survival (DDFS) for Dato-DXd + durvalumab vs ICT;DDFS for Dato-DXd vs ICT;DDFS for Dato-DXd + durvalumab vs Dato-DXd;Overall Survival (OS) for Dato-DXd + durvalumab vs ICT;OS for Dato-DXd vs ICT;iDFS for Dato-DXd vs ICT;iDFS for Dato-DXd + durvalumab vs Dato-DXd;Participant-reported physical function in participants treated with Dato-DXd with or without durvalumab compared with ICT;Participant-reported in GHS/QoL in participants treated with Dato-DXd with or without durvalumab compared with ICT;Participant-reported fatigue in participants treated with Dato-DXd with or without durvalumab compared with ICT;Pharmacokinetics of Dato-DXd;Immunogenicity of Dato-DXd;Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)