Comparison of Pretreatment with Sacituzumab Govitecan (SG) vs. SG + Pembrolizumab in Triple-Negative Breast Cancer with a Low Risk of Relapse (ADAPT-TN-III)

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer in which the tumor cells do not express hormone receptors (estrogen and progesterone) or HER2 receptors on their surface. These three surface proteins are key targets for targeted drug therapies. When they are absent, as in TNBC, many drugs cannot be effective. This characteristic makes TNBC difficult to treat and increases the risk of recurrence. The standard treatment for early-stage TNBC typically consists of neoadjuvant chemotherapy, followed by surgery to remove the tumor. The cancer is considered early-stage when the tumor is confined to the breast and has not spread to lymph nodes or other organs (Stage I or selected cases of Stage II). Intensive chemotherapy usually involves combinations of drug classes such as anthracyclines, taxanes, and platinum. However, these intensive treatments are often associated with numerous side effects.

The study drug sacituzumab govitecan is what is known as an antibody-drug conjugate. This means it consists of an antibody that recognizes and binds to the TROP-2 (trophoblast cell surface antigen 2) protein on the surface of cancer cells. It is coupled with a chemotherapeutic agent, which can thus act directly within the tumor cell. TROP-2 is particularly common on cells of TNBC tumors. This could be a gentler yet highly effective alternative treatment option, particularly for patients with a lower risk of recurrence or for older patients for whom intensive chemotherapy is not an option. The drug is already approved for advanced or metastatic TNBC. In early-stage disease, treatment has so far only been approved within the context of clinical trials. Pembrolizumab is a so-called PD-1 antibody that activates the body’s own immune system to fight cancer cells more effectively and can improve the treatment’s efficacy.

The goal of the ADAPT-TN-III trial is to determine whether pretreatment (over 12–18 weeks) with the antibody-drug conjugate sacituzumab govitecan —either alone or in combination with the immunotherapy pembrolizumab—achieves results comparable to those of conventional intensive chemotherapy regimens but with fewer side effects. Treatment is administered before surgery (neoadjuvant) in four cycles of three weeks each (12 weeks total) and can be extended by two additional cycles (6 weeks) in cases of incomplete response. Surgical tumor removal is then performed. Patients are randomly assigned to two groups. One group receives sacituzumab govitecan alone, while the other receives pembrolizumab in addition. The study is open-label, meaning that both patients and physicians know which treatment is being administered in each case. The primary endpoint of the study is to improve the rate of pathological complete remission (pCR)—that is, the complete disappearance of tumor cells in the tissue following pretreatment. Following treatment, patients will be monitored for up to three years to assess relapses or long-term effects.

Eligible participants include women and men aged 18 and older with newly diagnosed, early-stage TNBC (Stage I or selected cases of Stage II) without lymph node involvement and without metastases, which has not yet been treated. Participants must be in good general health and have adequate organ function. Pregnant or breastfeeding women, as well as patients with other cancers or severe comorbidities such as autoimmune diseases, are excluded from participation.