A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer

Inclusion Criteria:

• Participant must be ≥ 18 years, at the time of signing the ICF.

• Histologically confirmed Stage II or III unilateral or bilateral primary invasiveTNBC or hormone receptor-low/HER2-negative breast cancer

• ECOG PS of 0 or 1

• Provision of acceptable tumor sample

• Adequate bone marrow reserve and organ function

• Contraceptive use by males or females should be consistent with local regulationsregarding the methods of contraception for those participating in clinical studiesand aligned with protocol requirements.

Exclusion criteria:

• History of any prior invasive breast malignancy

• History of another primary malignancy except for malignancy treated with curativeintent with no known active disease within 5 years before randomization.

• active or prior documented autoimmune or inflammatory disorders.

• Evidence of distant disease.

• Clinically significant corneal disease.

• Has active or uncontrolled hepatitis B or C virus infection.

• Known HIV infection that is not well controlled.

• Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals;suspected infections; or inability to rule out infections.

• Known to have active tuberculosis infection

• Mean resting corrected QTcF interval > 470 ms obtained from ECG

• Uncontrolled or significant cardiac disease.

• History of non-infectious ILD/pneumonitis

• Has severe pulmonary function compromise

• Any prior or concurrent surgery, radiotherapy or systemic anticancer therapy forTNBC or hormone receptor-low/HER2-negative breast cancer

• For females only: is pregnant (confirmed with positive serum pregnancy test) orbreastfeeding, or planning to become pregnant.

• Female participants should refrain from breastfeeding from enrolment throughout thestudy and for at least 7 months after last dose of study intervention, or asdictated by local PI for SoC if longer.

• Concurrent use of systemic hormone replacement therapy or oral hormonalcontraception