CLINICAL TRIAL / NCT06103864

Key Inclusion Criteria - Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP guidelines. - ECOG PS 0 or 1. - All participants must provide a FFPE tumour sample (primary, metastatic (location excluding bone), or locally recurrent inoperable tumour sample) collected ≤ 3 months prior to signing of informed consent (ie, start of screening). - PD-L1 positive TNBC based on results from an appropriately validated investigational PD-L1 (22C3) assay (CPS ≥ 10) from a sponsor designated central laboratory. - No prior chemotherapy or targeted systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer. - Patients with recurrent disease will be eligible if they have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months have elapsed between completion of treatment with curative intent and the first documented recurrence. - Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin). - Measurable disease as per RECIST 1.1. - Adequate bone marrow reserve and organ function. - Male and female participants of childbearing potential must agree to use protocol-specified method(s) of contraception. Key Exclusion Criteria - 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.