A Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

The drug being tested in this study is called ixazomib. Ixazomib was being tested to treat
people who had newly diagnosed multiple myeloma who had not previously received systemic
treatment. This study was conducted in two Phases. Phase 1 looked at side effects and lab
results in people who took ixazomib to determine the MTD and RP2D. Phase 2 looked at overall
response rates and side effects in people who took ixazomib.

The study enrolled 15 patients in Phase 1 and 50 patients in Phase 2. Participants in Phase 1
were assigned to cohorts and received ixazomib 1.68, 2.23, 2.97, or 3.95 mg/m^2 in addition
to dexamethasone 40 mg and lenalidomide 25 mg. Participants in Phase 2 received ixazomib 4.0
mg fixed dose in addition to dexamethasone 40 mg and lenalidomide 25 mg. In both Phases study
treatment was administered in 28-day Cycles as follows: ixazomib Days 1, 8 and 15,
dexamethasone Days 1, 8, 15 and 22, and lenalidomide 25 mg Days 1 through 21.

This multi-center trial was conducted in the United States. The overall time to participate
in this study was 12, 28-day cycles with the option to continue into a maintenance portion in
the absence of disease progression or unacceptable toxicity. Participants made multiple
visits to the clinic and a final visit 30 days after last dose of study drug for a follow-up
assessment.

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

- Nonsecretory 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 systemic 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 or tolerance of ixazomib

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