UGN-201 for the Treatment of Bladder Cancer in Patients Undergoing Radical Cystectomy

Inclusion Criteria

• Scenario 1: Muscle invasive bladder cancer (MIBC): Histologically confirmed, by MD Anderson pathologic review, diagnosis of muscle invasive bladder cancer (cT2 ). No planned systemic chemotherapy prior to radical cystectomy by standard practice risk stratification, patient refusal, and/or patient ineligibility
• Scenario 2: Non-muscle invasive bladder cancer (NMIBC): Histologically confirmed, by MD Anderson pathologic review, diagnosis of non-muscle invasive bladder cancer (cT1 or less). No planned systemic chemotherapy prior to radical cystectomy by standard practice risk stratification, patient refusal, and/or patient ineligibility. Prior intravesical therapies, whether Bacillus Calmette-Guerin (BCG), chemotherapy or otherwise, will remain eligible
• Be willing and able to provide written informed consent
• Be >= 18 years of age
• Have histological confirmation of predominant urothelial cancer (either non-muscle invasive or muscle invasive). Patients whose tumors are found to be invasive should not have stage 3 or greater disease
• Have absence of metastatic disease as determined by conventional imaging studies and be considered a good surgical candidate by the treating physician
• Be willing to participate in the collection of blood, tissue, stool, and urine for banking and future correlative studies
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 14 days of treatment initiation)
• Platelets >= 100,000/mcL (performed within 14 days of treatment initiation)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency within 7 days of assessment (performed within 14 days of treatment initiation)
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 14 days of treatment initiation)
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 14 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN (performed within 14 days of treatment initiation)
• Albumin >= 2.5 mg/dL (performed within 14 days of treatment initiation)
• International normalized ratio(INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 14 days of treatment initiation)
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 14 days of treatment initiation)
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 30 days after the last dose of study medication * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 30 days after the last dose of study therapy * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Patients must consent to the MD Anderson Immunotherapy Platform laboratory protocol PA13-0291

Exclusion Criteria

• Is currently participating and receiving UGN-201 or has participated in a study of an investigational agent and received UGN-201 or used an investigational device within 4 weeks of the first dose of study treatment
• Has >= cT3 and/or cN+ and/or cM+ urothelial carcinoma of the bladder, non-predominant urothelial carcinoma or histologic variants, such as small cell, carcinosarcoma, squamous cell or adenocarcinoma
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Has a known history of active TB (Bacillus tuberculosis)
• Has a known history of hypersensitivity to UGN-201 or any of its excipients
• Has had prior systemic anti-cancer therapy for the treatment of bladder cancer. Prior intravesical therapies, whether BCG, chemotherapy or otherwise, will remain eligible Has cT3 or bulkier urothelial carcinoma of the bladder
• Has any other malignancy diagnosed within 2 years of screening with the exception of basal or squamous cell skin cancer, or non-invasive cancer of the cervix, or any other cancer deemed by the treating physician to be of low risk for progression or patient morbidity during the study period
• Has known metastatic disease as determined by conventional staging studies
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has a clinically significant active infection requiring systemic therapy and cannot be resolved prior to initiating treatment
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating physician
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Clinically significant urethral stricture that would preclude passage of a urethral catheter
• History of pelvic radiotherapy
• History of neurogenic bladder
• History of active urinary retention
• History of any other condition that would prohibit normal voiding
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 agent
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Has received a vaccine within 30 days of initiation of study therapy. Exceptions will be made for inactivated seasonal influenza and COVID-19 vaccines at the discretion of the treating physician. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed under any circumstances