Neoadjuvant Darolutamide Alone or in Combination With Standard Therapy for Stage II-IIIA, AR+, TNBC
A Phase II Neoadjuvant Clinical Trial of the Androgen Receptor Inhibitor Darolutamide in Early-Stage Androgen Receptor Positive (AR+) Triple-Negative Breast Cancer
Vandana Abramson
51 participants
Sep 9, 2025
INTERVENTIONAL
Conditions
Summary
This phase II trial compares the effect of adding darolutamide to standard therapy versus standard therapy alone before surgery for the treatment of patients with stage II-IIIA androgen receptor positive triple-negative breast carcinoma. Standard therapy before surgery for triple-negative breast cancer typically consists of a combination of chemotherapy and immunotherapy drugs. Chemotherapy drugs, such as carboplatin, paclitaxel, doxorubicin and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Darolutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Giving darolutamide in combination with standard therapy before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed.
Eligibility
Inclusion Criteria19
- Signed and dated written informed consent as well as the ability to understand and the willingness to sign written consent prior to study registration
- Male or female ≥ 18 years of age on the day of signing informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologically confirmed newly diagnosed breast cancer with the following requirements:
- \<10% staining for estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemistry (IHC)
- HER2 negative by fluorescence in situ hybridization (FISH)
- AR positive: defined as ≥ 80% staining for AR by IHC
- Primary tumor clinically or radiographically ≥ 1cm in size or stage II-IIIA and eligible for neoadjuvant treatment
- Absolute neutrophil count (ANC) ≥ 1500/µL (≤ 28 days prior to first dose of protocol-indicated treatment)
- Platelets ≥ 100,000/µL (≤ 28 days prior to first dose of protocol-indicated treatment)
- Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (≤ 28 days prior to first dose of protocol-indicated treatment)
- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (as calculated by the Cockcroft-Gault Formula or calculated/measured by an alternative established institutional standard consistently applied across participants at the site) (≤ 28 days prior to first dose of protocol-indicated treatment)
- Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), or direct bilirubin ≤ ULN for participants with total bilirubin \> 1.5 x ULN (≤ 28 days prior to first dose of protocol-indicated treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 times institutional upper limit of normal (ULN) (≤ 28 days prior to first dose of protocol-indicated treatment)
- Calcium ≤ 11.5 mg/dL or ≤ 2.9 mmol/L; in patients with albumin outside the normal range, calcium (corrected for albumin) must be ≤ 11.5 mg/dL or ≤ 2.9 mmol/L (≤ 28 days prior to first dose of protocol-indicated treatment)
- Women must not be breastfeeding and further agree to not breastfeed during study treatment and for at least 120 days after completion of treatment
- A woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test during screening within 21 days prior to receiving first dose of protocol-indicated treatment, and must agree to follow instructions for using acceptable contraception from the time of signing consent, and until at least 120 days after completion of treatment
- Men must refrain from donating sperm for at least 120 days after completion of treatment
- A man able to father children who is sexually active with a WOCBP must agree to follow instructions for using acceptable contraception, from the time of signing consent, and until at least 120 days after completion of treatment
Exclusion Criteria11
- Non-resectable breast cancer as assessed by the primary treating surgeon or evidence of metastatic disease
- Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastases or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer)
- Patient is pregnant or breastfeeding
- Patients with moderate hepatic impairment (Child-Pugh Class B cirrhosis or higher)
- Is currently participating in or within four weeks prior to receiving first dose of study treatment in a study of an investigational agent or investigational device
- Participants who have entered the follow-up phase of an investigational study may participate as long as it has been four weeks after the last dose or last exposure to the previous investigational agent or investigational device
- Recipient of previous allogeneic tissue/solid organ transplant
- Known severe hypersensitivity (≥ Grade 3) to study drug, pembrolizumab, carboplatin, doxorubicin/epirubicin, paclitaxel, or cyclophosphamide and/or any of the excipients of these drugs
- History of myocarditis or pericarditis or other known underlying heart disease that is clinically significant by investigator judgment (for example, cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III or IV, symptomatic arrhythmia not controlled by medication, unstable angina, history of acute myocardial infarction). History of cerebrovascular accident (including transient ischemic attack \[TIA\]) within the past six months (24 weeks) prior to starting study treatment
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection/sepsis, or psychiatric illness/social situations that would limit compliance with study requirements
- Known conditions that would preclude the use of checkpoint inhibitors
Interventions
Undergo blood sample collection
Undergo breast biopsies
Given IV
Given IV
Given PO
Given IV
Given IV
Undergo MRI
Given IV
Given IV
Undergo breast surgery
Undergo US
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07016399