A Phase 1 Study Evaluating AMG 232 in Advanced Solid Tumors or Multiple Myeloma

Study Design: This is an open-label, dose exploration study evaluating AMG 232 in subjects
with advanced p53WT solid tumors or multiple myeloma. The study will be conducted in 2 parts:
Part 1 - Dose Exploration (parts 1a, 1b and 1c) and Part 2 - Dose Expansion. Part 1a is aimed
at evaluating the safety, tolerability, PK and PD of AMG 232 and determining the MTD of a
7-day once daily (QD) dosing schedule in subjects with advanced solid tumors using a
practical continuous reassessment method (CRM). Part 1b will evaluate the safety and
tolerability of 3-day QD dosing schedule (or alternate dosing schedule based upon emerging
data) with a particular emphasis on evaluating the tolerability of daily doses equal to or
higher than the part 1a MTD in subjects with solid tumors or multiple myeloma. Part 1c will
evaluate the safety and tolerability of 7-day twice daily (BID) dosing schedule with daily
cumulative doses equal to or higher than the part 1a MTD in subjects with solid tumors. The
dose expansion part of the study (Part 2) can open once the MTD has been determined in Part
1a. Part 2, part 1b and part 1c can be explored in parallel. The dose expansion part will
consist of up to 85 additional subjects with specific tumors harboring MDM2 amplification
(liposarcoma [LPS], gliobastoma [ GBM ] and all other solid tumors) or potentially harboring
MDM2 overexpression (ER+ metastatic breast cancer) and a group of subjects with multiple
myeloma.

Inclusion Criteria:

- Men or women > 18 years old

- Pathologically documented, definitively diagnosed, advanced solid tumor that is
refractory to standard treatment, or which no standard therapy is available, or the
subject refuses standard therapy or multiple myeloma

- Willing to undergo pre-dose core needle tumor biopsies or bone marrow aspirate for
subjects with multiple myeloma.

- Ability to take oral medications and willing to record daily adherance to
investigational product

- Adequate hematological, renal, hepatic, and coagulation laboratory assessments

Exclusion Criteria:

- Active brain metastases

- For solid tumor-History or presence of hematological malignancies unless curatively
treated with no evidence of disease for greater than or equal to 5 years

- Active infection requiring intravenous (IV) antibiotics

- Anti-tumor therapy

- Therapeutic or palliative radiation therapy within 30 days of starting treatment

- Currently enrolled in another investigational device or drug study