An Open-label, Phase 1 Study of the Relative Bioavailability, Food Effect, Safety and Tolerability of MLN8237 in Patients With Advanced Solid Tumors

Inclusion Criteria:

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

- 18 years or older

- Histologically or cytologically confirmed metastatic and/or advanced solid tumor

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Female patients who are post menopausal, surgically sterile, or agree to practice 2
effective methods of contraception or abstain from heterosexual

- Male patients who agree to practice effective barrier contraception or agree to
abstain from heterosexual intercourse

- Voluntary written consent

- Suitable venous access for study-required blood sampling

- Measurable disease

- Recovered from effects of prior antineoplastic therapy

Exclusion Criteria:

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

- Female patients who are pregnant or lactating

- Serious medical or psychiatric illness that could interfere with protocol completion

- Major surgery within 14 days of first dose of MLN8237

- Antineoplastic therapy, radiation therapy or any experimental therapy 21 days prior
to first dose of MLN8237

- Nitrosoureas or mitomycin-C within 6 weeks before the first dose of MLN8237.

- Autologous stem cell transplant within 3 months before the first dose of MLN8237, or
prior allogeneic stem cell transplant at any time.

- Active infection requiring systemic therapy, or other serious infection

- Inability to swallow oral medication

- Gastrointestinal (GI) disease or GI procedure that could interfere with oral
absorption or tolerance of MLN8237

- Symptomatic brain metastasis

- Uncontrolled cardiovascular condition

- Diagnosis or treatment of another malignancy within 2 years preceding first dose of
study drug except nonmelanoma skin cancer or in situ malignancy completely resected

- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
hepatitis C

- Lactose-intolerant (Parts A and B only)

- Prior history of metabolic acidosis (Parts A and B only)

- Use of enzyme-inducing antiepileptic drugs such as phenytoin, carbamazepine or
phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days
prior to the first dose of MLN8237

- A medical condition requiring use of pancreatic enzymes; or daily, chronic , or
regular use of proton pump inhibitors (PPI); or histamine (H2) receptor antagonists.
Patients who intermittently use these medications must meet the following:

- No use of PPI within 7 days of first dose of MLN8237

- No use of H2 antagonist or pancreatic enzymes within 24 hours of first dose of
MLN8237

- Patients requiring full systemic anticoagulation