A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

This study will examine the safety and anticancer activity of enfortumab vedotin given
intravenously to patients with locally advanced or metastatic urothelial cancer who
previously received a CPI and either previously received platinum-containing chemotherapy
(Cohort 1) or are platinum-naïve and cisplatin-ineligible (Cohort 2). Patients who received
platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of
completion will be considered platinum-naïve. Approximately 100 patients are expected to be
enrolled in each cohort. The primary goal of the study is to determine the confirmed ORR of
enfortumab vedotin.

Inclusion Criteria:

- Histologically documented urothelial carcinoma (squamous differentiation or mixed cell
types allowed).

- Metastatic disease or locally advanced disease that is not resectable.

- Must have received prior treatment with a CPI in the locally advanced or metastatic
urothelial cancer setting. A CPI is defined as a programmed cell death protein 1
(PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI
therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease
either during therapy or within 3 months of therapy completion are eligible.

- Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or
be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment
(Cohort 2).

- Must have had progression or recurrence of urothelial cancer during or following
receipt of most recent therapy.

- Tumor tissue samples must be available for submission to the sponsor prior to study
treatment.

- Must have measurable disease according to Response Evaluation Criteria in Solid Tumors
(RECIST) (Version 1.1).

- An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort
1 or ≤2 for Cohort 2.

- Anticipated life expectancy of ≥3 months as assessed by the investigator.

Exclusion Criteria:

- Ongoing sensory or motor neuropathy Grade ≥2.

- Active central nervous system (CNS) metastases.

- Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.

- Prior enrollment in an enfortumab vedotin study or prior treatment with other
monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).

- Uncontrolled tumor-related pain or impending spinal cord compression.