Neoadjuvant Pembrolizumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing
Subjects with cT2-T3N0M0 urothelial cancer of the bladder will be enrolled. After completing two cycles of pembrolizumab, subjects will undergo a restaging MRI of the abdomen and pelvis with a standard acquisition protocol (as outlined in the protocol) as well as CT chest. A CT of the abdomen and pelvis may be performed if there are contraindications to MRI. Patients will also undergo a restaging cystoscopy and biopsies/TURBT as outlined in the protocol. Patients achieving a clinical complete response to treatment (defined in the protocol) will proceed with maintenance single agent pembrolizumab followed by surveillance. All other patients will proceed with standard of care local therapy as per their treating physicians followed by adjuvant pembrolizumab.
⁃ Subject must meet all of the following applicable inclusion criteria to participate in this study:
• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤ 1 within 28 days prior to registration.
• Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder. Clinical stage cT2-3N0M0. N0 will be considered the absence of radiographically enlarged lymph nodes on baseline imaging. Patients with lymph nodes \<1 cm in long axis on imaging may be eligible but must be discussed with the sponsor investigator.
• Have undergone a standard of care maximal transurethral resection of bladder tumor ≤ 60 days prior C1D1. Maximal TURBT is defined as a macroscopically complete resection of bladder tumor when safely possibly per the treating urologist. Patients who cannot safely undergo maximal TURBT as per their treating urologist are eligible for enrollment but should be discussed with the sponsor investigator.
• All subjects must have adequate transurethral resection of bladder tumor tissue available for submission (i.e., at least 15 unstained slides or paraffin block) identified during screening. This tissue can be from the maximal restaging TURBT, a prior diagnostic TURBT revealing muscle-invasive bladder cancer, or both specimens. Subjects without available archival tissue must be discussed with the sponsor-investigator.
• Decline cisplatin-based neoadjuvant chemotherapy or be considered cisplatin-ineligible based on at least one of the following modified criteria (as ECOG 0-1 is required for eligibility):
‣ Creatinine clearance \< 60 mL/min (but ≥ 30 mL/min)
⁃ Grade ≥ 2 hearing loss (per CTCAE criteria v5)
⁃ Grade ≥ 2 neuropathy (per CTCAE criteria v5)
⁃ New York Heart Association Class III heart failure
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
‣ Hematological
• Absolute Neutrophil Count (ANC): ≥ 1.5 x 10\^9/L
∙ Hemoglobin (Hgb): ≥ 9 g/dL
∙ Platelets: ≥ 100 x 10\^9/L
⁃ Renal
• Creatinine OR: Creatinine ≤ 1.5 × ULN OR
∙ Calculated creatinine clearance: creatinine clearance ≥ 30 mL/min
⁃ Hepatic
• Bilirubin: ≤ 1.5 ×ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 × ULN
∙ Aspartate aminotransferase (AST): ≤ 2.5 × ULN
∙ Alanine aminotransferase (ALT): ≤ 2.5 × ULN
• Women of childbearing potential (WOCP) must have a negative serum or urine pregnancy test a maximum of 24-hours before 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. WOCBP must agree to use contraception.
• A male participant must agree to use contraception.