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)

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 surgicalresection following neoadjuvant therapy.

4. Completed at least 6 cycles of neoadjuvant therapy containing an anthracyclineand/or a taxane with or without platinum chemotherapy, with or withoutpembrolizumab.

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 weeksprior to randomisation.

8. All participants must provide an FFPE tumour sample from residual invasive diseaseat 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 weeksbetween the completion of radiation therapy and the date of randomisation (radiationtherapy can be completed during screening period). If no post-operative radiationtherapy is given, an interval of no more than 16 weeks between the date of breastsurgery 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 perinvestigator 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 followingpreoperative therapy and surgery.

3. Severe or uncontrolled medical conditions including systemic diseases, history ofallogeneic organ transplant and active bleeding diseases, ongoing or activeinfection, serious chronic gastrointestinal conditions associated with diarrheachronic diverticulitis or previous complicated diverticulitis.

4. History of another primary malignancy except for adequately resected basal cellcarcinoma of the skin or squamous cell carcinoma of the skin, in situ disease (including ductal carcinoma in situ) that has undergone potentially curativetherapy, or other solid malignancy treated with curative intent with no known activedisease within 5 years before randomisation and of low potential risk forrecurrence.

5. Persistent toxicities caused by previous anticancer therapy, excluding alopecia, notyet improved to Grade ≤ 1 or baseline. Participants with irreversible toxicity thatis 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 thatrequired steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitisthat 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 torandomisation.

19. Participants with a known severe hypersensitivity to Dato-DXd or any of theexcipients of these products including but not limited to polysorbate 80 or othermonoclonal 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 investigationalmedicinal device administered in the last 4 weeks prior to randomisation,randomisation into a prior Dato-DXd, T-DXd, or durvalumab study regardless oftreatment assignment.

22. Currently pregnant (confirmed with positive pregnancy test), breastfeeding orplanning to become pregnant.