TROPION-Breast05: This study will assess how safe and effective an Dato-DXd (which is an antibody-drug conjugate), with or without immunotherapy, is compared with the standard care of chemotherapy plus immunotherapy in participants with PD-L1 positive locally recurrent inoperable or metastatic triple negative breast cancerA Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel or Gemcitabine + Carboplatin) in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer

Exclusion

• As judged by investigator, severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, significant cardiac or psychological conditions.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before Cycle 1 Day 1 and of low potential risk for recurrence.

• Neoplastic spinal cord compression or active brain metastases, leptomeningeal carcinomatosis or history of leptomeningeal carcinomatosis.

  - Participants with treated clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.

• Uncontrolled infection requiring IV antibiotics, antivirals or antifungals.
• Active or uncontrolled hepatitis B or C virus infection.
• Known HIV infection that is not well controlled.
• Uncontrolled or significant cardiac disease.
• History of non-infectious ILD/pneumonitis (including radiation pneumonitis) that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Severe pulmonary function compromise.
• Clinically significant corneal disease.
• Active or prior documented autoimmune or inflammatory disorders.
• Prior exposure to any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I and TROP2-targeted therapy.
• Any concurrent anti-cancer treatment.
• Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or Dato-DXd.
• Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.