Pembrolizumab (MK-3475) as First-line Therapy for High Risk T1 Non-Muscle-Invasive Bladder Cancer

Inclusion Criteria:

- Be willing and able to provide written informed consent/assent for the trial.

- Histologically confirmed urothelial cancer by TURBT performed at MSKCC.

- TURBT within 6 weeks of protocol entry with complete resection of all papillary
lesions.

- Patients with high risk, BCG-naïve non-muscle-invasive urothelial cancer defined as
having one of the following disease states:

- T1 on restaging biopsy, plus cis

- Multiple (≥ 1) T1 recurrences, plus cis

- Multifocal T1 plus cis

- T1b, plus cis

- T1 with lymphovascular invasion plus cis

- Patient refusal of cystectomy and bilateral pelvic lymphadenectomy

- No prior intravesical therapy.

- No prior radiation therapy for bladder cancer. Prior radiation therapy for prostate
cancer is allowed.

- ECOG performance status 0 or 1.

- Age ≥ 18 years of age

- Female subjects of childbearing potential should be willing to use 2 methods of birth
control, be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of the study medication (reference
section 9.5.2). Subjects of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for >1 year.

- Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through 120 days after the last dose of study therapy.

- Patients must not have other invasive malignancies within the past 5 years (with the
exception of non-melanoma skin cancers, localized prostate cancer, and carcinoma in
situ of the cervix).

- Required Initial Laboratory Values:

- Absolute neutrophil count ≥ 1.5 x 10E9/L

- Platelets ≥ 100 x 10E9/L

- Hemoglobin ≥ 9 g/dL

- Bilirubin ≤ 1.5 times the upper limit of normal (x ULN)

- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN

- Calculated creatinine clearance ≥ 30 using the CKD-Epi formula

Exclusion Criteria:

- Prior treatment with systemic chemotherapy

- Unstable angina

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- History of myocardial infarction within 6 months

- History of stroke within 6 months

- Evidence of bleeding diathesis or coagulopathy

- Presence of any systemic metastases (ie, nodal, visceral, or central nervous system)

- Major surgical procedure (other than TURBT) within 28 days prior to the study

- Pregnant (positive pregnancy test) or lactating

- Serious, non-healing wound, ulcer, or bone fracture

- Inability to comply with study and/or follow-up procedures

- Prior therapy with an anti-PD-1 agent, anti-PD-L1 agent, or other inhibitory or
stimulatory agent oriented towards a T-cell receptor

- Active infection requiring systemic therapy

- Known history of human immunodeficiency virus (HIV)

- Known active Hepatitis B or Hepatitis C

- Received live attenuated vaccines within 30 days prior to start of study treatment.
Patients must also agree to avoid live attenuated vaccines during study treatment.

- Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic or immunosuppressive agents. Subjects with vitiligo, diabetes Type
I, or resolved childhood asthma/atopy would be an exception to this rule. Subjects
that require intermittent use of bronchodilators, inhaled steroids, or local steroid
injections would not be excluded from the study. Subjects with hypothyroidism stable
on hormone replacement or Sjøgren's syndrome will not be excluded from the study.