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)

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.

What this study is about