Primary Outcomes:

Primary Outcome 1 - Measure: Pathologic Complete Response (pCR) Rate in All Participants

Primary Outcome 1 - Time Frame: Up to approximately 4 months (Time of surgery)

Primary Outcome 2 - Measure: Pathologic Complete Response Rate in Participants Whose Tumors Express PD-L1 Combined Positive Score (CPS) ≥10

Primary Outcome 2 - Time Frame: Up to approximately 4 months (Time of surgery)

Primary Outcome 3 - Measure: Event-Free Survival (EFS) in All Participants

Primary Outcome 3 - Time Frame: Up to approximately 5.5 years

Primary Outcome 4 - Measure: Event-Free Survival in Participants Whose Tumors Express PD-L1, CPS ≥10

Primary Outcome 4 - Time Frame: Up to approximately 5.5 years

Condition:

• Urinary Bladder Cancer, Muscle-invasive

Eligibility

Criteria:
Inclusion Criteria:

- Have a histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0)
with predominant (≥50%) urothelial histology (histology and presence of muscle invasion to
be confirmed by BICR): Participants with mixed histology are eligible provided the
urothelial component is ≥50%.

Participants whose tumors contain any neuroendocrine component are not eligible.

Urothelial carcinomas not originating from the bladder (e.g., upper tract [ureters, renal
pelvis], urethra) are not eligible.

- Have clinically non-metastatic bladder cancer (N0M0) determined by imaging (computed
tomography (CT) chest or magnetic resonance imaging (MRI) of the abdomen/pelvis.

- Be deemed eligible for RC + PLND by his/her urologist and/or oncologist and agree to
undergo curative intent standard RC + PLND (including prostatectomy if applicable).

- Have a transurethral resection (TUR) of a bladder tumor that is submitted and adequate
to determine histology, muscle invasion, and PD-L1 status by central pathology vendor.

- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Have demonstrated adequate organ function.

Exclusion Criteria:

- Has a known additional malignancy that is progressing or has required active
anti-cancer treatment ≤3 years of study randomization with certain exceptions.

- Has received any prior systemic anti-neoplastic treatment for MIBC.

- Is cisplatin-ineligible, as defined by meeting any one of the study criteria.

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX-40, CD137).

- Has received therapy with hematopoietic growth factor such as granulocyte-colony
stimulating factor (G-CSF) or granulocyte-monocyte-colony stimulating factor(GM-CSF)
in 14 days prior to randomization.

- Has received prior systemic anti-cancer therapy including investigational agents
within 3 years of randomization.

- Has received any prior radiotherapy to the bladder.

- Has received a live vaccine within 30 days prior to the first dose of study drug.

- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention.

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior the first dose of
study drug.

- Has hypersensitivity to monoclonal antibodies (mAbs, including pembrolizumab) and/or
any of their excipients.

- Has severe hypersensitivity (≥Grade 3) to cisplatin and/or gemcitabine and any of
their excipients.

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.

- Has an active infection requiring systemic therapy.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No