Adjuvant Sacituzumab Govitecan and Nivolumab in Muscle-Invasive Urothelial Carcinoma at High-Risk Recurrence

Eligibility 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, including radical cystectomy or nephroureterectomy.
• * Radiographic disease-free status as determined by imaging within 28 days of C1 D1 of study treatment.
• * Prior platinum-based neoadjuvant chemotherapy (NAC) is allowed. If chemotherapy-naive, patient must be Cisplatin-ineligible (based on Galsky et al 2011 \[10\]) or refuse platinum adjuvant chemotherapy.
• * 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 the radical cystectomy or nephroureterectomy surgical specimen.
• * 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 the radical cystectomy or nephroureterectomy surgical specimen.
• * 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 ≤ 1.3 × institutional ULN
• * Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
• * Female subjects of childbearing potential must not be pregnant following signing the study consent form.
• * Recovery to ≤ Grade 1 of CTCAE version 5 toxicities related to any prior treatment for UC, unless AE(s) is clinically non-significant and/or stable on supportive therapy as per discretion of the Investigator.
• * Ability to understand and the willingness to sign a written informed consent.
• * Underwent a partial cystectomy or partial nephrectomy.
• * History of adjuvant platinum-based chemotherapy or any other type of adjuvant therapy 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 or other immunosuppressive medications within 14 days of study treatment initiation.
• * 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.
• * 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.
• * Uncontrolled intercurrent illness.
• * Received a live vaccine within 30 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.