Brief Title: Study of Sacituzumab Govitecan (IMMU-132) in Metastatic or Locally Advanced Unresectable Urothelial Cancer

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Overall Survival (OS)

Primary Outcome 1 - Timeframe: Up to 3.5 years

CONDITION

• Locally Advanced or Metastatic Unresectable Urothelial Cancer

ELIGIBILITY

Key Inclusion Criteria:
Individuals with histologically documented metastatic or locally advanced unresectable UC defined as
Tumor (T) 4b, any node (N) or

- Any T, N 2-3 Tumors of upper and lower urinary tract are permitted. Mixed histologic types are allowed if urothelial is the predominant histology.

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
Individuals with progression or recurrence following receipt of platinum-containing regimen and anti programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) therapy for metastatic or locally advanced unresectable disease will be enrolled.
a. Individuals with recurrence or progression ≤12 months following completion of cisplatin-containing chemotherapy given in the neo-adjuvant/adjuvant setting may utilize that line of therapy to be eligible for the study. The 12-month period is counted from completion of surgical intervention or platinum therapy, respectively. These individuals must receive anti PD-1/PD-L1 therapy in the metastatic or locally advanced unresectable setting to be eligible.

- b. Individuals who received either carboplatin or anti PD-1/PD-L1 therapy in the neo- adjuvant/adjuvant setting will not be able to count that line of therapy towards eligibility for the study.
c. Cisplatin ineligible individuals who meet one of the below criteria and who were treated with carboplatin in the metastatic or locally advanced unresectable settings may count that line of therapy towards eligibility. They must then have received anti PD-1/PD-L1 therapy in metastatic or locally advanced unresectable setting to be eligible for the study.
Cisplatin ineligibility is defined as meeting one of the following criteria:
1. Creatinine Clearance < 60 mL/min - 2. Grade ≥ 2 Audiometric Hearing Loss - 3. Grade ≥ 2 Peripheral Neuropathy - 4. New York Heart Association (NYHA) Class III heart failure - 5. ECOG PS ≥ 2 - d. Anti PD-1/PD-L1 therapy administered as part of maintenance therapy may be counted towards eligibility for the study - e. Individuals who have progressed after receiving enfortumab vedotin in prior lines of therapy, and individuals who are either ineligible or unable to tolerate enfortumab vedotin therapy, are eligible to enroll in the study - f. Individuals who received only concurrent chemoradiation for bladder preservation without further systemic therapy are not eligible to enroll in the study. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen and no progression was noted prior to the change in platinum. - Individuals with previously treated brain metastases may participate in the study provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and stabilization of all neurologic symptoms, have no evidence of new or enlarging brain metastases, and are not using steroids >20 mg of prednisone (or equivalent) daily for brain metastases for at least 7 days prior to first dose of the study drug.

- Adequate hematologic counts without transfusion or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥1,500/mm^3, and platelets ≥100,000/µL).
Adequate hepatic function (bilirubin ≤1.5x institutional upper limit of normal (IULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases and serum albumin >3 g/dL).
Docetaxel will only be option in TPC arm for Individuals with a total bilirubin ≤1 x IULN, and an AST and/or ALT ≤1.5x IULN if alkaline phosphatase is also >2.5 x IULN.
Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation or other validated instruments (e.g. Modification of Diet in Renal Disease (MDRD) equation).

- Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

- Females of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study drug. Individuals of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years.

- Males must agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy.
Key Exclusion Criteria:
Females who are pregnant or lactating.

- Have had a prior anti-cancer monoclonal antibody (mAb)/ antibody-drug conjugate (ADC) within 4 weeks prior to Cycle 1 Day 1 (C1D1) or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Individuals participating in observational studies are eligible.

- Have received prior chemotherapy for UC with any available SOC therapies in the control arm (i.e., both prior paclitaxel and docetaxel in regions where vinflunine is not an approved therapy, or prior paclitaxel, docetaxel and vinflunine in regions where vinflunine is approved and is commercially available).
Have not recovered (i.e., ≤ Grade 1) from AEs due to previously administered chemotherapeutic agent.
Note: Individuals with ≤ Grade 2 neuropathy or any grade of alopecia are an exception to this criterion and will qualify for the study.

- Note: If Individuals received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy.

- Have previously received topoisomerase 1 inhibitors.
Have an active second malignancy.
• Note: Individuals with a history of malignancy that have been completely treated and with no evidence of active cancer for 3 years prior to enrollment, or individuals with surgically cured tumors with low risk of recurrence are allowed to enroll in the study after discussion with the medical monitor.
Have active cardiac disease, defined as:
Myocardial infarction or unstable angina pectoris within 6 months of C1D1.

- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.

- NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of <40%. - Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of enrollment. - Have an active serious infection requiring anti-infective therapy (Contact medical monitor for clarification). - Have known history of Human Immunodeficiency Virus (HIV)-1/2 with undetectable viral load and on medications that may interfere with SN-38 metabolism. - Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In individuals with a history of HBV or HCV, individuals with a detectable viral load will be excluded. - Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations. - Have inability to tolerate or are allergic to any potential TPC agent or sacituzumab govitecan-hziy or unable or unwilling to receive the doses specified in the protocol. - Have inability to complete all specified study procedures for any reason.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Gilead Study Director

Role: Study Director

Affiliation: Gilead Sciences

Overall Contact

Name: Gilead Study Director

Phone: 1-833-445-3230(GILEAD-0)

Email: GileadClinicalTrials@gilead.com

LOCATION