A Phase III, Open-label, Randomised Study of Neoadjuvant Datopotamab Deruxtecan (Dato-DXd) Plus Durvalumab Followed by Adjuvant Durvalumab With or Without Chemotherapy Versus Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab With or Without Chemotherapy for the Treatment of Adult Patients With Previously Untreated Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer.
Primary:
- 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 receptorlow/ HER2-negative breast cancer, by central assessment of pCR.
- 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 receptorlow/ HER2-negative breast cancer, by investigator assessment of EFS.
Secondary:
- 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 receptorlow/ HER2-negative breast cancer, by assessment of OS.
- To assess effectiveness 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 receptorlow/ HER2-negative breast cancer, by assessment of DDFS.
- To assess participant-reported breast and arm symptoms in participants with previously
untreated TNBC or hormone receptorlow/ HER2-negative breast cancer treated with neoadjuvant Dato-DXd plus durvalumab relative to neoadjuvant pembrolizumab plus chemotherapy.
- To assess participant-reported physical function in participants with previously untreated TNBC or hormone receptorlow/ HER2-negative breast cancer treated with 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.
- To assess participant-reported fatigue in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer treated with 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.
- To assess participant-reported GHS/QoL in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer treated with 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.
- To assess the PK of Dato-DXd, total anti-TROP2 antibody and DXd (in combination with durvalumab).
MEDI4736 (Durvalumab)
Pembrolizumab (MK-3475)
- RWJBarnabas Health
- Community Medical Center
- Cooperman Barnabas, Livingston
- Jersey City Medical Center, Jersey City
- Monmouth Medical Center
- Monmouth Medical Center Southern Campus
- Robert Wood Johnson University Hospital, Hamilton
- Robert Wood Johnson University Hospital, Somerset
- Rutgers University
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. Exclusion criteria: - History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before randomization and of low potential risk for recurrence. - 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 - Resting ECG with clinically significant abnormal findings. - Uncontrolled or significant cardiac disease. - History of non-infectious ILD/pneumonitis - 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.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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