Breast Cancer D926QC00001

The primary objectives of the study are to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor low/HER2-negative breast cancer, by central assessment of pCR and/or to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer, by investigator assessment of EFS

Inclusion Criteria:

  • Participant must be ≥ 18 years, at the time of signing the ICF.
  • Stage II or III unilateral or bilateral primary invasive TNBC 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 regulations regarding the methods of contraception for those participating in clinical studies and aligned with protocol requirements.

Exclusion criteria:

  • History of any prior invasive breast malignancy
  • History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 5 years before randomization.
  • active or prior documented autoimmune or inflammatory disorders.
  • 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
  • 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 for TNBC or hormone receptor-low/HER2-negative breast cancer
  • For females only: is pregnant or breastfeeding, or planning to become pregnant.
  • Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of study intervention, or as dictated by local PI for SoC if longer.
  • Concurrent use of systemic hormone replacement therapy or oral hormonal contraception

Locations: HH, Manchester, Avon, HOCC, MMC, SVMC

Contacts: Rebecca O'Doherty 860.972.5371 Rebecca.O'[email protected]; Carissa Tipping 860.827.6061 [email protected]

Sponsor: AstraZeneca

Cancer Clinical Research Office