Dose Escalation Study of MLN1117 in Subjects With Advanced Cancer

Inclusion Criteria:

- Subjects have had their PIK3CA gene mutation status assessed prior to enrolling into
the study

- Subjects must have documented disease progression prior to enrolling into the study

- locally advanced or metastatic solid tumors with the exception of primary brain
tumor, and have failed or are not eligible for standard of care therapy.

- Age ≥ 18 years, including males and females;

- ECOG performance status (PS) 0-1;

- Adequate organ function;

- Male subjects must be surgically sterile or must agree to use physician-approved
contraception during the study and for 30 days following the last study drug
administration;

- Ability to swallow oral medications;

- Ability to understand and willingness to sign informed consent prior to initiation of
any study procedures;

- For women of child-bearing potential, negative serum pregnancy test within 14 days
prior to the first study drug administration and use of physician-approved method of
birth control from 30 days prior to the first study drug administration to 30 days
following the last study drug administration

Exclusion Criteria:

- Diagnosis of primary brain tumor; untreated brain metastasis or history of
leptomeningeal disease or spinal cord compression;

- Received prior cancer or other investigational therapy within 2 weeks prior to the
first administration of study drug;

- Have received a systemic corticosteroid within one week prior to the first
administration of study drug;

- Clinically significant cardiac disease;

- Myocardial infarction or unstable angina within 6 months prior to the first
administration of study drug;

- Malabsorption ;

- Poorly controlled diabetes mellitus;

- Pregnancy (positive serum or urine pregnancy test) or breast feeding;

- Untreated brain metastasis or history of leptomeningeal disease or spinal cord
compression;

- Failed to recover from the reversible effects of prior anticancer therapies;

- Have received a selective PI3K-alpha inhibitor

- Other clinically significant co-morbidities, such as uncontrolled pulmonary disease,
active central nervous system (CNS) disease, active infection, or any other condition
that could compromise the subject's participation in the study

- Known human immunodeficiency virus (HIV) infection

- Have a secondary malignancy within the last 3 years prior to first dose of study
drug, excluding treated non-melanoma skin cancer, carcinoma in situ, or
locally-treated prostate cancer