ASG-15ME is a Study of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

Inclusion Criteria:

* Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
* Part A: Subject must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy.
* Part B: Subject must not have received any prior lines of chemotherapy in the metastatic setting (prior treatment with immunotherapy is allowed).
* Part C (CPI-Treated Expansion): Subject must have received prior treatment with a CPI in the metastatic setting
* Subjects must have measureable disease according to RECIST (version 1.1).
* Part A and C: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Part B: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Life expectancy of ≥ 3 months
* Adequate hematologic function
* Parts A and C: Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min
* Part B: Renal function, as follows: creatinine clearance estimate ≥ 15 mL/min and \<60 mL/min by Cockcroft Gault equation adjusted for body weight
* Adequate liver function

Exclusion Criteria:

* Preexisting sensory neuropathy Grade ≥ 2 or motor neuropathy Grade ≥ 2
* Uncontrolled central nervous system metastases
* Use of any investigational drug within 14 days prior to the first dose of study drug
* Any anticancer therapy, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)
* Subjects with Immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible
* Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug
* History of thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug
* Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication
* Known HIV or AIDS
* Positive Hepatitis B surface antigen test
* Positive Hepatitis C antibody test
* Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
* Known sensitivity to any of the ingredients of the investigational product AGS15E
* Major surgery within 28 days prior to first dose of study drug
* History of a primary invasive malignancy not listed in the inclusion criteria, which has not been in remission for at least 3 years. The following are exempt from the 3 year limit:

  * Non-melanoma skin cancer;
  * adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is undetectable;
  * cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap smear; and
  * definitively treated, stage I/II ER+ breast cancer
* Active infection requiring treatment ≤ 7 days before first dose of study drug
* History of uncontrolled diabetes mellitus or diabetic neuropathy
* Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
* Has ocular conditions such as:

  * Active infection or corneal ulcer (e.g., keratitis)
  * Monocularity
  * History of corneal transplantation
  * Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
  * Uncontrolled glaucoma (topical medications allowed)
  * Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder