• Age ≥18 years at the time of consent.

• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Able and willing to provide written informed consent.

• Eastern Cooperative Oncology Group scores ≤ 1 within 28 days prior to registration.

• Non-muscle-invasive bladder cancer

‣ Cohort A: CIS +/- high grade papillary urothelial cancer (Ta or T1) after 3-mo evaluation after induction BCG.

⁃ Cohort B: High grade papillary urothelial cancer (Ta or T1) after 3-mo evaluation after induction BCG.

• Mixed variant histology (adenocarcinoma, squamous cell carcinoma) is eligible, but pure variant histology is ineligible. NOTE: Pathology report required for documentation purposes.

• Persistent disease (defined as not achieving disease free status) after completing therapy with at least induction BCG (≥ 5 doses) and the first round of maintenance or second induction course (≥ 2 doses). The subsequent round of BCG, either maintenance or repeat induction, must be given within 6 months of initial induction BCG.

‣ Persistent high risk NMIBC (T1, high grade papillary urothelial cancer Ta and/or CIS) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above.

• High grade T1 after completing therapy with at least induction BCG (≥ 5 doses) or after completing therapy with at least induction BCG (≥ 5 doses) and first round of maintenance or second induction course (≥ 2 doses). The subsequent round of BCG, either maintenance or repeat induction, must be given within 6 months of initial induction BCG.

‣ Disease recurrence (T1) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above.

• Patients who are disease free at 6 months after starting BCG but have high grade recurrence (T1, Ta, CIS) while on maintenance therapy would be eligible.

‣ The recurrence must be within 6 months of the last BCG dose.

• NMIBC patients, with high grade recurrence, having received adequate BCG within 24 months of last BCG exposure, are eligible.

⁃ Patients may have received up to 1 line of prior therapy (6 cycles of induction chemotherapy) for NMIBC after BCG (NOTE: prior PD-1/PD-L1 blockade is prohibited).

⁃ Patients must be deemed unfit for radical cystectomy by the treating physician or refuse radical cystectomy. NOTE: Reason for being deemed unfit or refusal should be documented in the medical record.

⁃ All visible tumor must be completely resected within 60 days prior to registration (residual pure CIS is permitted).

∙ All patients must have had a cystoscopy (or TURBT with complete resection) without papillary tumor and negative urine cytology within 28 days prior to registration (positive cytology is allowed in patients with CIS).

⁃ All patients with T1 tumors must undergo restaging TURBT within 60 days prior to registration.

∙ There must be uninvolved muscularis propria in the restaging TURBT specimen.

‣ The initial TURBT prior to the restaging TURBT may be \> 60 days prior to registration.

⁃ Patients must have baseline tumor tissue from either initial or repeat TURBTs for submission of a minimum of 2 and up to 10 unstained slides for translational study objectives. If archival tissue is not available, the subject is not eligible.

⁃ Adequate organ function as defined by ALL of the following within 28 days prior to registration:

∙ Absolute neutrophil count ≥ 1500/µL

‣ Platelets ≥ 100,000/µL

‣ Hemoglobin ≥ 9 g/dL

‣ Aspartate aminotransferase/alanine aminotransferase ≤ 1.5× upper limit of normal (ULN)

‣ Total serum bilirubin ≤ 1.5×ULN\*; \*Patients with Gilbert's disease: ≤ 3×ULN

‣ International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN unless the patient is on therapeutic anticoagulation.

‣ Creatinine clearance ≥ 40 mL/min by Cockcroft-Gault estimation. The patient's estimated CrCl will be calculated by the local laboratory (for eligibility purposes) using screening/baseline height (m), actual weight (kg), and serum creatinine:

⁃ Males: CrCl = ((140 - age in years) × weight (kg)) / (72× serum creatinine (mg/dL)) Females: CrCl = ((140 - age in years) × weight (kg) ×0.85) / (72× serum creatinine (mg/dL))

⁃ Females of childbearing potential (FOCBP) must have a negative urine or serum pregnancy test within 7 days of registration. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required. FOCBP must agree to use contraception during the study.

⁃ Men capable of fathering a child must agree to use contraception during the study.

⁃ Must have a life expectancy of at least 12 weeks.