AMG 172 First in Human Study in Patients With Kidney Cancer

This First in- human study of AMG 172 will be conducted in two parts: Part 1 (dose
exploration) and Part 2 (dose expansion). Part 1 of the study is aimed at evaluating the
safety, tolerability and PK of AMG 172 given every two weeks and every three weeks in
subjects with relapsed / refractory cc RCC, and Part 2 is aimed at evaluating safety,
tolerability, PK and response rate in subjects treated at the MTD established in Part 1 for
either every two week or every three week dosing. Up to 48 subjects may be enrolled in Part
1, and up to 30 subjects may be enrolled in Part 2. The dose of AMG 172 utilized in Part 2
will be dependent upon data obtained in Part 1 of the study.

Inclusion Criteria:

- Subjects must have a pathologically documented, definitively diagnosed, clear cell
RCC that is relapsed/refractory following at least two lines of systemic therapy (one
of which must be a tyrosine kinase), or the subject refuses standard therapy

- Measurable disease per RECIST 1.1 criteria. Subjects with non-measurable, but
evaluable disease are also eligible for Part 1 of the study.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

- Willing to provide tumor samples and / or slides

- Hematological function, as follows:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L;

2. Platelet count ≥ 100 x 10^9/L;

3. Hemoglobin > 9 g/dL

- Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 x institutional
upper limit of normal (IULN)

- Hepatic function, as follows:

1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x ULN;

2. Total bilirubin < 1.5 x ULN (< 3.0 x ULN for subjects with documented Gilbert's
Disease or for whom the indirect bilirubin level suggests an extrahepatic source
of elevation);

3. Alkaline phosphatase < 2 x ULN (< 5 x ULN in subjects whom the PI and sponsor
agree that clinical data suggest extrahepatic source of elevation)

- Other inclusion criteria may apply

Exclusion Criteria:

- Known primary central nervous system (CNS) tumors or brain metastases

- History of bleeding diathesis

- Myocardial infarction within 6 months of study day 1, symptomatic congestive heart
failure (New York Heart Association > class II), unstable angina, or unstable cardiac
arrhythmia requiring medication, or uncontrolled hypertension in the opinion of the
investigator

- Clinically significant ECG changes which obscure the ability to assess the PR, QT,
and QRS interval; congenital long QT syndrome

- A baseline ECG QTcF > 470 msec

- Known positive test for human immunodeficiency virus (HIV)

- Known acute or chronic hepatitis B or hepatitis C infection as determined by
serologic tests

- Other exclusion criteria may apply