We are doing this study to test the safety and effectiveness of the study drug, datopotamab deruxtecan (also known as dato-DXd), and find out if it is a potential option for patients with metastatic breast cancer that has spread to the brain and/or spinal cord.

HER2-Negative Metastatic Breast Cancer with Central Nervous System (Brain and Spinal Cord) Metastases

Adults ages 18+ who:

• Are diagnosed with metastatic breast cancer that is HER2-negative
• Have radiological confirmation of metastatic disease to the brain and/or spinal cord

For more information, contact the study team at 919-684-5301.

As part of this study, participants will be enrolled into one of three cohorts:

• Cohort A will include participants with estrogen receptor (ER)-positive HER2-negative breast cancer.
• Cohort B will include participants with metastatic triple negative breast cancer.
• Cohort C will include participants with HER2-negative metastatic breast cancer that has spread to the leptomeninges (the tissue surrounding the brain or spinal cord).

If you choose to join this study, regardless of your assigned cohort, you will receive the study drug intravenously (IV) for as long as you get a positive benefit. You will get the drug in 21-day periods called "cycles," and you will be evaluated after each cycle. After the study regimen ends, we will check in with you every 6 months for the remainder of your life.