Sacituzumab Govitecan and Pembrolizumab Therapy before Surgery for the Treatment of Immunochemotherapy-Resistant Early-Stage Triple-Negative Breast Cancer

Inclusion Criteria

• Female or male patients 18 years of age or older.
• Histologically or cytologically confirmed breast cancer.
• T1c N1-2 or T2-4 N0-2 early-stage disease.
• Estrogen receptor (ER)/progesterone receptor (PR) negative (ER/PR <1%) or ER/PR low positive (1%<ER/PR<10%), and human epithelial growth factor receptor 2 (HER2) negative as per institutional and American Society of Clinical Oncology College of American Pathologists (ASCO-CAP) guidelines.
• Initiated the neoadjuvant chemotherapy (NAC) with the first regimen of KN-522 regimen (i.e., pembrolizumab 200 mg every 3 weeks (Q3W), given with 4 cycles of paclitaxel + carboplatin).
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
• Suboptimal response to the first part of the KN-522 regimen (carboplatin + paclitaxel + pembrolizumab), defined as disease progression during or .80% reduction in tumor volume after 4 cycles of carboplatin + paclitaxel + pembrolizumab. Except in the case of disease progression, assessment of volume reduction for purposes of eligibility needs to be conducted after completion of 4 cycles of carboplatin + paclitaxel + pembrolizumab. Cases where assessment of volume reduction for purposes of eligibility are conducted prior to completion of 4 cycles of carboplatin + paclitaxel + pembrolizumab (defined as 12 weekly doses of taxane-based therapy) due to extenuating circumstances (e.g. toxicity or patient logistical reasons) can be considered on a case by case basis upon discussion with the PI of the study.
• Negative serum pregnancy test within 72 hours of receiving the first dose of the study medication for women of childbearing potential as per institutional guidelines. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo pregnancy tests.
• Agreed with undergoing the image-guided core needle biopsy after completing the first part of neoadjuvant treatment regimen.
• Subjects of childbearing potential should be willing to use effective birth control methods or be surgically sterile or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of the study drug. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Effective methods of birth control include: * Use hormonal birth control methods: pills, shots/injections, implants (placed under the skin by a health care provider), or patches (placed on the skin). * Intrauterine devices (IUDs). * Using 2 barrier methods (each partner must use 1 barrier method) with a spermicide. Males must use the male condom (latex or other synthetic material) with spermicide. Females must choose either a Diaphragm with spermicide, cervical cap with spermicide, or a sponge.
• Absolute neutrophil count >= 1,500 /uL
• Platelets >= 100,000 /uL * Hematologic counts above should be without transfusion within 2 weeks of study drug initiation.
• Hemoglobin >= 9 g/dL * Hematologic counts above should be without transfusion within 2 weeks of study drug initiation.
• Creatinine clearance >= 50 ml/min.
• Total bilirubin =< 1.5 X upper limit of normal (ULN).
• Alanine aminotransferase and aspartate aminotransferase =< 2.5 X ULN.

Exclusion Criteria

• Stage IV disease.
• Any other previous antitumor therapies for the current cancer event.
• Pregnant or planning to become pregnant during therapy.
• Gastrointestinal tract disease or defect or previous history of colitis.
• Has an active autoimmune disease that requires systemic therapy within two years of treatment or a medical condition that requires immunosuppression.
• Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
• Has known human immunodeficiency virus (HIV) infection or active hepatitis B or C infection (screen test is not required). Subjects positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
• Has a cognitive impairment.
• Any other major comorbidities that can impact receiving immunotherapy or sacituzumab govitecan.
• Have live vaccinations within 30 days prior to registration and receive study treatment.