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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Primary Objective

Primary Outcome 1 - Timeframe: 6 months after last patient enrollment

CONDITION

• Urothelial Carcinoma
• Muscle-invasive Bladder Cancer

ELIGIBILITY

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Nataliya Mar, MD

Role: Principal Investigator

Affiliation: Chao Family Comprehensive Cancer Center

Overall Contact

Name: Chao Family Comprehensive Cancer Center University of California, Irvine, University of California Irvine Medical

Phone: 1-877-827-8839

Email: [email protected]

LOCATION