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

About

Brief Summary

This is a Phase III, 2-arm, randomised, open-label, multicentre, global study assessing the efficacy and safety of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy compared with 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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 3

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

Inclusion Criteria:

Participant must be ≥ 18 years, at the time of signing the ICF.
Histologically confirmed 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.
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 for TNBC or hormone receptor-low/HER2-negative breast cancer
For females only: is pregnant (confirmed with positive serum pregnancy test) 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