Keynote-905: This phase III trial is evaluating a type of bladder surgery alone and in combination with immunotherapy (Pembrolizumab) in patients with muscle-invasive bladder cancerA Phase 3 Randomized Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer

Exclusion

• Known additional nonurothelial malignancy that is progressing or has required active anticancer treatment ≤3 years of study randomization, with certain exceptions
• Has ≥ N2 or metastatic disease (M1) as identified by imaging
• Received any prior systemic treatment, chemoradiation, and/or radiation therapy for for muscle-invasive bladder cancer (MIBC) or non-muscle invasive bladder cancer (NMIBC)
• Received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• Received prior systemic anticancer therapy including investigational agents within 3 years prior to randomization
• Received any prior radiotherapy to the bladder
• Received a partial cystectomy of the bladder to remove any non-muscle-invasive bladder cancer (NMIBC) or MIBC
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Current participation in or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of study intervention
• Ongoing sensory or motor neuropathy Grade 2 or higher
• Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
• Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
• Severe hypersensitivity (≥ Grade 3) to enfortumab vedotin or any excipient contained in the drug formulation of enfortumab vedotin
• Active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator
• Active autoimmune disease that has required systemic therapy in 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) is not considered a form of systemic therapy and is allowed
• Has uncontrolled diabetes
• History of (noninfectious) pneumonitis that required steroids, or current pneumonitis
• Active infection requiring systemic therapy
• Has had an allogeneic tissue/solid organ transplant