MLN8237 in Adults With Nonhematological Malignancies, Followed by MLN8237 in Lung, Breast, Head and Neck or Gastroesophageal Malignancies

Following the determination of the Recommended Phase 2 Dose (RP2D) and schedule (Phase 1),
20 response-evaluable patients in each of the 5 tumor indications will be enrolled (Phase
2-Stage 1). An interim analysis will determine which tumor indications will proceed to
enroll an additional 25 patients (Phase 2-Stage 2) to further evaluate Overall Response Rate
(ORR) and other secondary endpoints.

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
(Phase 1 only)

- Phase 2 requires Non-small cell lung cancer (NSCLC); Small-cell lung cancer; Breast
adenocarcinoma (female patients only); Squamous cell cancer of the head and neck
(HNSCC); or Gastroesophageal adenocarcinoma

- 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 intercourse

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

- Voluntary written consent

- Wiling to comply with scheduled visits, treatment plan, laboratory tests and other
trial procedures

- Measurable disease (Phase 2 only)

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

- Receipt of more than 2 previous cytotoxic chemotherapeutic regimens (4 previous
regimens for breast cancer). There is no limit on the number of prior noncytotoxic
therapies

- Prior treatment with Aurora A-targeted agents, including MLN8237

- Prior treatment with high-dose chemotherapy

- Prior allogeneic bone marrow or other organ transplant

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

- Symptomatic brain metastasis

- Radiotherapy to greater than 25% of bone marrow

- 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

- Myocardial infarction within 6 months of enrollment

- Uncontrolled cardiovascular condition

- Major surgery within 14 days of first dose of MLN8237

- Active infection requiring systemic therapy, or other serious infection

- Inability to swallow oral medication

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

- Patients requiring full systemic anticoagulation

- History of uncontrolled sleep apnea syndrome

- Treatment with clinically significant enzyme inducers within 14 days prior to the
first dose of MLN8237 and during the study