Inclusion Criteria:
* Age ≥ 18 years at the time of study consent.
* ECOG Performance Status of 0, 1 or 2 (see Appendix A).
* Histologically confirmed muscle-invasive UC originating in the bladder, ureter, or renal pelvis. Variant histology, except small cell carcinoma, is allowed.
* Underwent curative-intent surgery (i.e. RC or nephroureterectomy), performed within 180 days prior to study treatment initiation.
* Radiographic disease-free status as determined by imaging within 28 days of C1D1 of study treatment.
* Prior platinum-based NAC is allowed. If chemotherapy-naive, patient must be Cisplatin-ineligible (based on Galsky et al 2011 \[10\]) or refuse platinum AC.
* Prior treatment with neoadjuvant investigational agents is allowed (except PD-1/PD-L1 inhibitors or sacituzumab govitecan). No washout from neoadjuvant therapy is required.
* If NAC was given, patient must be considered at high risk for cancer recurrence due to having pathologic T2, T3, T4, or N+ disease on RC or nephroureterectomy surgical spec-imen.
* If no NAC was given, patient must be considered at high risk for cancer recurrence due to having pathologic T3, T4, or N+ disease on RC or nephroureterectomy surgical speci-men.
* Adequate organ and marrow function as defined below:
* ANC ≥ 1000/mcL
* Platelets ≥ 100,000/mcL
* Total bilirubin ≤ 1.5 × institutional ULN (or ≤ 3.0 × ULN for subjects with Gilbert's disease)
* AST/ALT ≤ 3 × institutional ULN
* Alkaline phosphatase ≤ 3 × institutional ULN
* Serum albumin ≥ 2.8 g/dL
* Creatinine Creatinine clearance of ≥30 mL/min (calculated with Cockroft-Gault formula)
* Hemoglobin ≥ 9.0 g/dL
* aPTT ≤ 1.5 × institutional ULN
* Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (i.e. barrier methods including male condom, female condom, or diaphragm with spermicidal gel, etc.) that are approved by the Investigator. Contra-ception must be used during the course of the treatment and for 6 months after the last dose of study treatment.
* Female subjects of childbearing potential must not be pregnant following signing the study consent form. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal sta-tus (defined as at least 12 months of amenorrhea in a woman ≥ 45 years-of-age in the ab-sence of other biological or physiological causes).
* Recovery to ≤ Grade 1 of CTCAE version 5 toxicities related to any prior treatment for UC, unless the AE(s) is clinically non-significant and/or stable on supportive therapy as per discretion of the Investigator.
* Subjects with any type of genitourinary catheters (i.e. nephrostomy, Foley, etc) are al-lowed.
* Ability to understand and the willingness to sign a written informed consent. Both men and women and members of all races and ethnic groups are eligible for this trial. Non-English speaking, hard of hearing, and illiterate individuals are eligible for this trial.
Exclusion Criteria
* Underwent a partial cystectomy or partial nephrectomy.
* History of adjuvant platinum-based chemotherapy or any other type of adjuvant therapy, including investigational agents, following surgical removal of UC.
* History of treatment with PD-1/PD-L1 inhibitors or sacituzumab govitecan prior to study treatment initiation.
* History of previous radiation therapy for treatment of UC.
* Radiographic evidence of metastasis.
* Receipt of or planning to receive any other concurrent investigational agents.
* History of active, known, or suspected autoimmune disease.
* Conditions requiring treatment with either systemic high-dose corticosteroids (e.g. prednisone dose of ≥ 10 mg or equivalent) or other immunosuppressive medications within 14 days of study treatment initiation.
* Inhaled or topical steroids are permitted in the absence of active autoimmune dis-ease.
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
* Major surgery within 28 days or minor surgery within 14 days before the first dose of study treatment. Subjects must have complete wound healing and resolution from complications of major or minor surgery before first dose of study treatment.
* Active malignancy within 3 years of study entry, except treated localized non-melanoma skin cancer, Gleason 6 prostate cancer on active surveillance, or curatively treated in situ cancer of the breast or cervix.
* Patients who do not have adequate organ and marrow function, as defined in Section 4.1 above.
* Uncontrolled intercurrent illness including, but not limited to, the following conditions:
* Active and/or uncontrolled bacterial, viral, or fungal infection within 7 days of study treatment initiation.
* History of HIV infection with detectable viral load.
* History of Hepatitis B or C infection with detectable viral load.
* History of severe liver impairment (Child-Pugh C liver cirrhosis).
* History of active tuberculosis (Bacillus tuberculosis).
* Congestive heart failure New York Heart Association (NYHA) Class 3 or 4, unstable angina pectoris, or serious uncontrolled cardiac arrhythmias.
* Stroke (including transient ischemic attack (TIA), myocardial infarction (MI), or other ischemic arterial event within 90 days before first dose of study treatment.
* Severe, uncontrolled bleeding within 14 days before first dose of study treatment.
* Uncontrolled diarrheal illness ≥ Grade 3 in severity within 14 days before first dose of study treatment.
* History of inflammatory bowel disease (i.e. ulcerative colitis, Crohn's disease, etc.) or any other condition that puts patients at high risk of developing severe diarrhea.
* Psychiatric illness/social situations causing inability to comply with study proce-dures or follow up.
* Pregnancy at the time of or following study consent.
* Breastfeeding at the time of or following study consent.
* Received a live vaccine within 28 days prior to the first dose of study treatment.
* Known or suspected severe hypersensitivity (Grade ≥ 3) to nivolumab, sacituzumab govitecan, irinotecan, and/or any of their components.
* History or current evidence of any condition, therapy, or laboratory/radiographic abnormal-ity that might confound the results of the study, interfere with the patient's ability to participate for the full duration of the study, or is not in the best interest of the patient to partici-pate in the study, in the opinion of the Investigator.
