An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of MLN9708, a Second-Generation Proteasome Inhibitor, Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment

Inclusion Criteria:

Each patient must meet all of the following eligibility criteria to be enrolled in the
study:

- Male or female patients 18 years or older

- Previously untreated multiple myeloma diagnosed according to standard criteria
requiring systemic treatment

- Patients must have measurable disease

- Nosecretory multiple myeloma based upon standard M-component criteria (i.e.,
measurable serum/urine M-component) is not allowed unless the baseline serum free
light chain level (Freelite™) is evaluated Patients must meet clinical laboratory
criteria as specified in study protocol

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

- Female and male patients MUST adhere to the guidelines of the lenalidomide pregnancy
prevention program

- Must be able to take concurrent aspirin 325 mg daily

- Voluntary written consent

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be enrolled in the
study:

- Peripheral neuropathy that is greater or equal to Grade 2

- Female patients who are lactating or pregnant

- Major surgery or radiotherapy within 14 days before the first dose of study drug

- Serious infection requiring systematic antibiotic therapy within 14 days before the
first dose of study drug

- Diarrhea greater than Grade 1 based on the National Cancer Institute Common
Terminology Criteria for Adverse Events

- Central nervous system involvement.

- Evidence of current uncontrolled cardiovascular conditions within the past 6 months

- Known human immunodeficiency virus (HIV) positive, hepatitis B surface
antigen-positive status, or known or suspected active hepatitis C infection

- Serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of treatment according to the protocol

- Known gastrointestinal condition that could interfere with swallowing or the oral
absorption of tolerance of MLN9708

- No other prior malignancy within 2 years except nonmelanoma skin cancer or carcinoma
in situ of any type if they have undergone complete resection