Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Multiple Myeloma, NHL, and AML

This is a first-in-human (FIH), multicenter, non-randomized, open-label, phase 1 study
evaluating AMG 397 administered orally once daily for 2 consecutive days followed by 5 days
break at a weekly interval, as part of a 28-day treatment cycle in adult subjects with
multiple myeloma, non-Hodgkin's lymphoma, and acute myeloid leukemia.

Inclusion Criteria:

- Subject has provided informed consent prior to initiation of any study-specific
activities/procedures

- Age ≥ 18 years old

- Pathologically-documented, definitively-diagnosed relapsed or refractory MM, NHL, or
AML and is intolerant to, or considered ineligible for available therapies known to
provide clinical benefit. -

MM subjects only: Measurable disease per the IMWG response criteria, as indicated by one or
more of the following: Serum M-protein ≥ 0.5 g/dL, Urine M-protein ≥ 200 mg/24 hours. For
Subjects who do not meet 1 of the 2 prior criteria: Serum Free Light Chain (sFLC) ≥ 10
mg/dL (≥ 100 mg/L) and an abnormal sFLC ratio (< 0.26 or > 1.65) as per the IMWG response
criteria

- NHL subjects only: Radiographically measurable disease with a clearly demarcated nodal
lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least
1.0 cm in its largest dimension

- AML subjects only: Pathologically confirmed diagnosis of AML as defined by the WHO
Classification, More than 5% blasts in bone marrow

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

- Able to swallow and retain orally administered medication and does not have any
clinically significant gastrointestinal abnormalities that may alter absorption

- Hepatic function, as follows: Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) < 3 x upper limit of normal (ULN), Total bilirubin (TBIL) < 1.5
X ULN (except subjects with Gilbert's syndrome)

- Cardiac function, as follows: Cardiac ejection fraction ≥ 50% and no evidence of
pericardial effusion as determined by an ECHO or MUGA, No clinically significant ECG
findings.

- Renal function as follows: Calculated or measured creatinine clearance (CrCl) of ≥ 30
mL/minute calculated using the formula of Cockcroft and Gault [(140 - Age) × Mass (kg)
/ (72 × serum creatinine mg/dL)]. Multiply result by 0.85 if female.

Exclusion Criteria:

- Previously received an allogeneic stem cell transplant within 6 months of study day 1
OR having signs or symptoms of acute or chronic graft-versus-host disease

- Autologous stem cell transplant < 90 days prior to study day 1

- Candidates for stem cell transplant should have failed or are not considered eligible
for either allogeneic and autologous transplant

- Myocardial infarction within 6 months of study day 1

- Symptomatic congestive heart failure (New York Heart Association > Class II)

- History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past 6
months prior to study day 1

- Infection requiring intravenous anti-infective treatments within 1 week of study day 1

- Known positive results for human immunodeficiency virus (HIV)

- Active hepatitis B and C based on the following results: Positive for hepatitis B
surface antigen (HBsAg) (indicative of chronic, hepatitis B or recent acute hepatitis
B), Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA
by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA
suggests occult hepatitis B. Positive Hepatitis C virus antibody (HCVAb): hepatitis C
virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic
hepatitis C

- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to
Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1, or to
levels dictated in the eligibility criteria with the exception of grade 2peripheral
neuropathy, alopecia or toxicities from prior anti-tumor therapy that are considered
irreversible (defined as having been present and stable for > 4 weeks prior to study
day 1 may be allowed if they are not otherwise described in the exclusion criteria AND
there is agreement to allow by both the investigator and sponsor)

- Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy,
retinoid therapy, or investigational agent or procedures) within 14 days of day 1

- Prior systemic radiation therapy must have been completed at least 28 days before
study day 1. Prior focal radiotherapy completed at 14 days before study day 1

- Males and females of reproductive potential who are unwilling to practice an
acceptable method(s) of effective birth control while on study through 3 months after
receiving the last dose of study drug. Acceptable methods of effective birth control
include sexual abstinence (males, females); vasectomy; bilateral tubal
ligation/occlusion; or a condom with spermicide (men) in combination with barrier
methods (diaphragm, cervical cap, or cervical sponge), hormonal birth control or IUD
(females)

- Females who are lactating/breastfeeding or who plan to breastfeed while on study
through 3 months after receiving the last dose of study drug

- Females with a positive pregnancy test or planning to become pregnant while on study
through 3 months after receiving the last dose of study drug

- Males who are unwilling to abstain from sperm donation while on study through 3 months
after receiving the last dose of study drug