The primary objective of this study is to assess overall survival (OS) with sacituzumab
govitecan-hziy in comparison with treatment of physician's choice (TPC) in participants with
metastatic or locally advanced unresectable urothelial cancer (UC).
1. 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.
2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
3. 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
- 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 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.
4. 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
5. Adequate hematologic counts without transfusion or growth factor support within 1 week
of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC)
≥1,500/mm^3, and platelets ≥100,000/µL).
6. 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.
7. 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).
8. 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.
9. 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.
10. Male individuals must agree to use an adequate method of contraception starting with
the first dose of study therapy through 3 months after the last dose of study therapy.
1. Females who are pregnant or lactating.
2. 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.
3. Have received prior chemotherapy for UC with all 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 an approved therapy).
4. Have not recovered (i.e., ≤ Grade 1) from AEs due to previously administered
- 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
5. Have previously received topoisomerase 1 inhibitors.
6. 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.
7. 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
- NYHA Class III or greater congestive heart failure or left ventricular ejection
fraction of <40%.
8. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)
or gastrointestinal (GI) perforation within 6 months of enrollment.
9. Have an active serious infection requiring anti-infective therapy (Contact medical
monitor for clarification).
10. Have known history of Human Immunodeficiency Virus (HIV)-1/2 with undetectable viral
load and on medications that may interfere with SN-38 metabolism.
11. 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.
12. 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.
13. 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.
14. Have inability to complete all specified study procedures for any reason.