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

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, including radical cystectomy or nephroureterectomy.

within 180 days prior to study treatment initiation.

• 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.

Exclusion Criteria

• 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.