This is a Phase III, global, multicenter, open-label randomized controlled trial in patients with metastatic or locally advanced unresectable urothelial cancer who have progressed after prior therapy with platinum-based regimen and anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy. Approximately 600 subjects from 123 global sites will be enrolled
This is a Phase III, global, multicenter, open-label randomized controlled trial in which
approximately 600 subjects with metastatic or locally advanced unresectable UC who have
progressed after prior therapy with platinum-based regimen and anti-programmed cell death
protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy will be randomized to either
sacituzumab govitecan arm or Treatment of Physician's Choice (TPC) arm.
Subjects in TPC arm will have 1 of 3 standard of care (SOC) chemotherapeutic options
including paclitaxel, docetaxel, and vinflunine. Subjects randomized to the sacituzumab
govitecan arm will receive 10 mg/kg of sacituzumab govitecan intravenously on Day 1 and Day 8
of 21-day cycles. Those randomized to the TPC arm will have the choice of receiving
paclitaxel, docetaxel, and vinflunine administered intravenously at SOC doses of 175, 75 and
320 mg/m2 respectively, on Day 1 of 21-day cycles.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||November 16, 2020||Phase 3||Interventional|
Primary Outcome 1 - Measure: Overall Survival (OS)
Primary Outcome 1 - Time Frame: Until study completion, up to 3.5 years
1. Female or male subjects, ≥18 years of age, able to understand and give written
2. Subjects with histologically documented metastatic or locally advanced unresectable UC
• 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.
3. ECOG performance status (PS) score of 0 or 1.
4. Subjects with progression or recurrence following receipt of platinum-containing
regimen and anti PD-1/PD-L1 therapy for metastatic or locally advanced unresectable
disease will be enrolled.
1. Subjects 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 subjects must receive anti PD-1/PD-L1 therapy in the
metastatic or locally advanced unresectable setting to be eligible.
2. Subjects 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.
3. Cisplatin ineligible subjects 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 Subjects 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.
5. Subjects 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.
6. 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/mm3, and platelets ≥100,000/µL).
7. 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 subjects 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.
8. 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).
9. Female subjects 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.
10. Female subjects 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. Subjects of childbearing
potential are those who have not been surgically sterilized or have not been free from
menses for >2 years.
11. Male subjects 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. Women who are pregnant or lactating.
2. Have had a prior anti-cancer mAb/ ADC within 4 weeks prior to C1D1 or have had prior
chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks
prior to C1D1. Subjects 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: Subjects with ≤Grade 2 neuropathy or any grade of alopecia are an exception
to this criterion and will qualify for the study.
- Note: If subjects 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: Subjects with a history of malignancy that have been completely treated and
with no evidence of active cancer for 3 years prior to enrollment, or subjects 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:
1. Myocardial infarction or unstable angina pectoris within 6 months of C1D1.
2. 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
3. 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 subjects with a
history of HBV or HCV, subjects 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 or unable or unwilling to receive the doses specified in the protocol.
14. Have inability to complete all specified study procedures for any reason.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Cabilia C. Pichardo, MD
Role: Study Director
Affiliation: Immunomedics, Inc.
Name: Dianne Nowicke, MS
|Univ of California Irvine
Orange, California 92868
|BRCR Medical Center
Plantation, Florida 33322
|Thompson Oncology Group
Knoxville, Tennessee 37916
|Univ of TN Medical Center
Knoxville, Tennessee 37920
|BRCR Medical Center
San Juan, 00907-1509