Clinical Trials Search at Vanderbilt-Ingram Cancer Center

Inclusion Criteria:

Pathologically confirmed residual invasive breast cancer, in the breast and/or lymph node(s), following neoadjuvant chemotherapy. In the absence of residual invasive disease in the breast, lymph node must contain at least 2 mm of invasive disease

HER2 negative in primary tumor pre-treatment by local pathology assessed according to current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines: * In situ hybridization non-amplified (ratio of HER2 to CEP17 2.0 or single probe average HER2 gene copy number 4 signals/cell), OR * Immunohistochemistry (IHC) 0 or IHC 1+ ** NOTE: If more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the principal investigator to establish eligibility

Estrogen receptor (ER) and progesterone receptor (PR) negative in primary tumor pre-treatment defined as 10% of cells expressing hormonal receptors via IHC analysis by local laboratory assessment

Patients must have received neoadjuvant chemotherapy prior to breast surgery

Patients must be within 4 months of completion of all locoregional therapy (either last surgery or last dose of radiation, whichever is later). Definitive breast surgery must have been performed and includes lumpectomy or mastectomy with pathologically clear margins (i.e. no ink on tumor). For patients undergoing lumpectomy, this must be followed by whole breast irradiation. Definitive surgery also includes axillary surgery, either sentinel lymph node biopsy or axillary lymph node dissection at the discretion of the attending surgeon

Evidence of ctDNA in blood sample collected after completion of all local and systemic neoadjuvant therapy (preoperative chemotherapy) surgery and radiation, confirmed by central testing. Detection of any tumor specific mutations (TSMs) within the sample will be considered positive for purposes of study eligibility

Concurrent receipt of bone modifying agents (bisphosphonates or rank-ligand inhibitors) is allowed

Prior treatment with an immune checkpoint inhibitor in the neoadjuvant setting is permitted

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Men and women, age >= 18 years

Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1500/uL) without granulocyte colony-stimulating factor support

White blood cell (WBC) count >= 2.5 x 10^9/L (2500/uL)

Absolute lymphocyte count >= 0.5 x 10^9/L (500/uL)

Platelet count >= 100 x 10^9/L (100,000/uL)

Hemoglobin >= 90 g/L (9.0 g/dL), with or without transfusion

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) = 2.5 x institutional upper limit of normal (ULN)

Serum bilirubin = 1.5 x institutional ULN with the following exception: * Patients with known Gilbert syndrome: serum bilirubin level = 3 x institutional ULN

Serum creatinine = 1.5 x institutional ULN

Creatinine clearance >= 30 mL/min as assessed by the Cockcroft-Gault equation

Serum albumin >= 25 g/L (2.5 g/dL)

For patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) = 1.5 x institutional ULN

For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

Women of childbearing potential (pre-menopausal) must have a negative serum or urine pregnancy test within 7 days prior to start of therapy. A woman is defined as pre-menopausal if she is less than 12 months from last menstrual period with no identified cause other than menopause (medication induced amenorrhea is not acceptable). Pregnancy test is not required in women who are surgically sterile via bilateral salpingo-oophorectomy or hysterectomy

Women of childbearing potential and men must agree to use adequate contraception for the duration of protocol treatment and for 6 months after last dose of atezolizumab and 6 months after last dose of sacituzumab govitecan, whichever is later. Hormonal contraceptives are not acceptable

Ability to understand and the willingness to sign a written informed consent document. Non-English speakers are eligible to participate but will be excluded from surveys/questionnaires unless the participant has a proxy available for translation



Exclusion Criteria:

Prior therapy with sacituzumab govitecan, irinotecan, or any topoisomerase I-containing antibody-drug conjugates at any time for early stage disease

Receipt of adjuvant chemotherapy (all chemotherapy prior to registration must have occurred in the preoperative setting); adjuvant pembrolizumab is allowed

Prior hypersensitivity to atezolizumab or the excipients of atezolizumab or sacituzumab govitecan

Clinical or radiographic evidence of metastatic disease

Residual ductal breast carcinoma in situ (DCIS) or lobular breast carcinoma in situ (LCIS) alone without invasive cancer OR pT0N0i and pT0N1mic residual disease

Concurrent enrollment on another investigational therapy trial

Prior treatment-related toxicity must be resolved to = grade 1, prior to study enrollment, with the exception of alopecia and peripheral neuropathy

Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study

Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study

Intercurrent illness including, but not limited to: ongoing or active infection requiring systemic therapy, active tuberculosis, serious liver disease such as cirrhosis, active bleeding diathesis, uncontrolled type I or type II diabetes mellitus, grade >= 2 uncontrolled or untreated hypercholesterolemia, hypertriglyceremia or hypercalcemia

Cardiovascular disease including: congestive heart failure of New York Heart Association class II or higher, myocardial infarction ( 6 months prior to enrollment) unstable angina pectoris, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease, in the opinion of the investigator

History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

Active (acute or chronic) autoimmune disease of any type except hypothyroidism on a thyroid-replacement hormone, celiac disease, or well-controlled psoriasis, eczema, lichen simplex chronicus or vitiligo

Impairment of gastrointestinal function or active gastrointestinal disease that may significantly alter the absorption of the study agents (e.g., ulcerative disease, uncontrolled nausea (>= grade 2), vomiting (>= grade 2), diarrhea (>= grade 2), malabsorption syndrome or small bowel resection)

Congenital long QT syndrome or screening QT interval corrected through use of Fridericias formula > 480 ms

Participants known to be positive for the human immunodeficiency virus (HIV), hepatitis B surface antigen (HepBsAg), or hepatitis C virus (HCV) ribonucleic acid (RNA) are ineligible

History of prior invasive breast cancer in either breast

Participants with history of prior malignancy other than breast cancer are eligible if they have been disease-free for at least 5 years prior to enrollment with the exception of patients with thyroid cancer that has been definitively treated without spread to regional lymph nodes

Treatment with strong UGT1A1 inhibitor or inducer within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug

Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine while on protocol treatment

Known allergy or hypersensitivity to any of the study drugs or any of their excipients, including chimeric or humanized antibodies or fusion proteins and Chinese hamster ovary cell products or recombinant human antibodies

Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions: * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study

Pregnant women are excluded from this study because the effects of sacituzumab govitecan and atezolizumab on a developing fetus are unknown. Breastfeeding should be discontinued prior to entry onto the study and for one month following the last dose of sacituzumab govitecan