Comparison of a New Combination Therapy (Sacituzumab Govitecan + Pembrolizumab) With Standard Chemotherapy Before Surgery for Early-Stage, Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a form of breast cancer in which the tumor cells express neither hormone receptors (estrogen/progesterone) nor HER2 receptors on their cell surfaces. This characteristic makes TNBC so difficult to treat, as the absence of these receptors means there are no key targets for therapy. Treatment typically begins before surgery (neoadjuvant) with chemotherapy to shrink the tumor, making it easier to operate on and helping to prevent the spread of cancer (metastases). Complete disappearance of the tumor in the tissue (pathological complete remission, “pCR”) is associated with very good long-term outcomes. The standard combination recommended in guidelines today includes pembrolizumab (immunotherapy) in addition to chemotherapy (taxane, anthracycline, and platinum); this regimen has been shown to achieve higher pCR rates and fewer relapses. The drug under investigation, sacituzumab govitecan, is an antibody-drug conjugate consisting of an antibody that specifically binds to cancer cells and delivers a cytotoxic agent into the tumor cells to inhibit their growth.

This Phase 3 study examines two scenarios. Cohort I (De-escalation): Stage 2 patients who have achieved a clinical complete response after approximately 12 weeks of standard therapy with carboplatin/taxane + pembrolizumab undergo surgery immediately. The study will assess whether similarly favorable outcomes can be achieved without further chemotherapy. The primary endpoint is event-free survival at 3 years.

Cohort II (Intensification): Stage 3 patients or Stage 2 patients who did not achieve a complete response after 12 weeks of standard therapy are randomly assigned and receive either sacituzumab govitecan + pembrolizumab or standard chemotherapy + pembrolizumab until surgery. The most important criteria are event-free survival at 3 years and the rate of pathological complete remissions (pCR) at the time of surgery.

Subsequent treatment is then determined based on the surgical findings. Sacituzumab govitecan is administered as an infusion on days 1 and 8 every 3 weeks. Pembrolizumab is infused every 3 weeks. The follow-up period per patient is designed to last approximately 3 years; the total duration of the study is planned to run through March 2033.

Eligible participants include women and men aged 18 and older with confirmed triple-negative breast cancer (TNBC) (or “TNBC-like”), stage 2–3, without distant metastases.