Atezolizumab + Sacituzumab Govitecan to Prevent Recurrence in TNBC (ASPRIA)

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 2mm of invasive disease.
• •HER2 negative in primary tumor pre-treatment by local pathology assessed according to current ASCO/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
• •ER and 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.
• •ECOG Performance Status of 0 or 1
• •Men and women, age ≥ 18 years
• •Adequate hematologic and organ function defined by the following:
• •* ANC ≥ 1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor support
• •* WBC count ≥ 2.5 × 109/L (2500/μL)
• •* Absolute Lymphocyte count ≥ 0.5 × 109/L (500/μL)
• •* Platelet count ≥ 100 × 109/L (100,000/μL)
• •* Hemoglobin ≥ 90 g/L (9.0 g/dL), with or without transfusion
• •* AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 × institutional upper limit of normal (ULN).
• •* Serum bilirubin ≤ 1.5 × institutional ULN with the following exception:
• •* Patients with known Gilbert syndrome: serum bilirubin level ≤ 3 × 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: INR or aPTT ≤ 1.5 × 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 premenopausal 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 salpingooophorectomy 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 (see section 5.6).
• •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.
• •Treatment with strong 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 anti-tumor 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. o 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.