A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4

The purpose of this study is to evaluate the safety and pharmacokinetics ASG-22CE as well as
assess the immunogenicity and antitumor activity in subjects with metastatic urothelial
cancer and other malignant solid tumors.

Eligibility Criteria

Inclusion Criteria:

- Dose Escalation: Histologically confirmed metastatic malignant solid tumors
(excluding sarcomas) that are resistant or have recurred

- Dose Refinement: Histologically confirmed metastatic urothelial cancer (including
mixed cell types) and bladder cancer of any histology that is resistant or has
recurred

- Subjects must have a tumor positive (Immunohistochemical (IHC) H-score ≥150) for
Nectin-4 expression (as measured by central laboratory using primary or metastatic
tumor tissue)

- Must have failed at least one prior chemotherapy regimen for metastatic disease
(urothelial and bladder cancer subjects are not required to have failed prior
chemotherapy if considered unfit for cisplatin-based chemotherapy)

- Subject must have documented disease progression if most recent systemic treatment
was with an investigational immunotherapy drug

- Subjects must have measurable disease according to RECIST (version 1.1)

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

- Life expectancy of ≥ 3 months

- Negative pregnancy test (women of childbearing potential)

- Hematologic function, as follows (no red blood cell or platelet transfusions are
allowed within 14 days of the first dose of ASG-22CE):

- Absolute neutrophil count (ANC) ≥ 1.0 x 10 9/L

- Platelet count ≥ 100 x 10 9/L

- Hemoglobin ≥ 9 g/dL

- Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour
creatinine clearance of ≥ 45 mL/min

- Total bilirubin < 1.5 x ULN (upper limit of normal)

- Serum albumin > 2.5 g/dL

- Aspartate aminotransferase (AST) ≤ 1.5 x ULN

- Alanine aminotransferase (ALT) ≤ 1.5 x ULN

- Gamma-glutamyl transpeptidase (Gamma GT) ≤ 1.5 x ULN

- International normal ratio (INR) < 1.3 or ≤ institutional ULN (or ≤ 3.0 if on
therapeutic anticoagulation)

- Sexually active fertile subjects, and their partners, must agree to use medically
accepted double-barrier methods of contraception (e.g., barrier methods, including
male condom, female condom, or diaphragm with spermicidal gel) during the study and
at least 6 weeks after termination of study therapy

- Competent to comprehend, sign, and date an independent ethics committee/institutional
review board/research ethics board (IEC/IRB/REB) approved informed consent form

Exclusion Criteria:

- Preexisting sensory neuropathy Grade ≥ 2

- Preexisting 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 within 14 days prior to the first dose of study drug,
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)

- Any P-glycoprotein (P-gp) inducers/inhibitors or strong cytochrome P4503A (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 Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome
(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 ASG-22CE

- 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 Prostate Specific Antigen (PSA) that is undetectable;

- cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap
smear; and

- definitively treated, stage I/II ER positive breast cancer

- History of uncontrolled diabetes mellitus or diabetic neuropathy

- Active infection requiring treatment ≤7 days before dose of study drug

- 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

- Any medical, psychiatric, addictive or other kind of disorder which compromises the
ability of the subject to give written informed consent and/or to comply with
procedures

Principal Investigator

Peter VanVeldhuizen

Study Contact

ctnursenav@kumc.edu, 913-945-7552

Estimated Completion Date

Monday, January 1, 2018

ClinicalTrials.gov #

NCT02091999
06/02/2015