This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug or a combination of investigational drugs to learn whether the drug or drug combination works in treating a specific disease. "Investigational" means that the drug or drug combination is being studied.

The U.S. Food and Drug Administration (FDA) has approved Sacituzumab Govitecan for metastatic triple-negative breast cancer, but it is currently approved only for patients who have had 2 or more prior regimens for metastatic disease. The U.S. Food and Drug Administration (FDA) has not approved Pembrolizumab for metastatic triple-negative breast cancer but it has been approved for other uses.

In this research study, we are:

• Studying Sacituzumab Govitecan alone or in combination with Pembrolizumab as a possible treatment for patients with metastatic triple-negative breast cancers that are PD-L1-negative.
• Sacituzumab Govitecan is composed of a chemotherapy drug, called Irinotecan, which is attached to an antibody. Antibodies are proteins normally made by the immune system that bind to substances that don't belong in the body to prevent harm. The antibody in this study binds to certain types of cancer tumors, including triple-negative breast tumors.
• Pembrolizumab is an immunotherapy, called an anti-PD-1 or a checkpoint inhibitor, and is an antibody (a type of human protein) designed to allow the body's own immune system to seek out and destroy tumors. It has been used in previous research studies to treat breast cancer, where it has been shown to be effective.
• The overall goal of this study is to evaluate the effectiveness of either Sacituzumab Govitecan alone or in combination with Pembrolizumab, in delaying the worsening of triple-negative breast cancers that are PD-L1-negative.

The research study procedures include: screening for eligibility, research blood collections, at least two research biopsies, paired research stool collections, questionnaires, data collection, and study treatment including evaluations and follow up visits.

Participants will be randomized into one of two groups.

• Group A: Sacituzumab Govitecan on days 1 and 8 and Pembrolizumab on day 1 of a 21-day cycle
• Group B: Sacituzumab Govitecan alone on days 1 and 8 of a 21-day cycle

Participants will receive study treatment for as long as they are benefitting from this therapy. Participants will be followed for the rest of their life.

It is expected that about 110 people will take part in this research study.