Phase 1b Study of MLN0128 in Combination With MLN1117 in Adult Patients With Advanced Nonhematologic Malignancies

Inclusion Criteria:

- Male or female patients 18 years or older

- Patients must have a diagnosis and documented disease progression of a solid tumor
malignancy, excluding primary brain tumor, for which standard, curative, or life
prolonging treatment does not exist or is no longer effective

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

- Female subjects who are postmenopausal for at least 1 year prior to screening. For
women of child-bearing potential agree to practice 2 effective methods of
contraception, or agree to practice true abstinence

- Male subjects must agree to practice effective barrier contraception during the entire
study treatment period and through 30 days after last dose of study drug or practice
true abstinence

- Voluntary written consent

- Suitable venous access

- Patients must have a block of banked tumor tissue and/or fresh tumor tissue or at
least 10 unstained slides available to be sent to the central laboratory

- Clinical laboratory values as specified in the protocol

- Patients must have radiographically or clinically evaluable tumor

Exclusion Criteria:

- Female patients who are lactating and breastfeeding or have a positive serum pregnancy
test during the Screening period or a positive urine pregnancy test on Day 1 before
first dose of study drug

- Any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of treatment

- Treatment with any investigational products within 30 days before the first dose of
study drug

- Previous treatment with MLN1117 and/or MLN0128; previous treatment with dual mTORC1/2
or dual PI3K-mTOR inhibitors

- Failed to have recovered from the reversible effects of previous anticancer therapies

- Have received systemic corticosteroid (inhalers are allowed) within 7 days before the
first administration of study drug

- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
absorption or tolerance of study drug

- Diagnosis of diabetes mellitus

- Other clinically significant co-morbidities, such as uncontrolled pulmonary disease,
active CNS disease, active infection

- Known human immunodeficiency virus (HIV) infection

- Cardiovascular conditions as defined in the protocol

- A requirement for positive inotropic support (excluding digoxin) or serious
uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation) within 1 year
before screening

- Patients who are taking proton pump inhibitors within 7 days of the first dose or who
require treatment with proton pump inhibitors during the trial or those who are taking
H2 receptor antagonists within 24 hours of the first dose

- Patients who received previous therapy with PI3K inhibitors or rapalogs will be
allowed in the study if all other inclusion/exclusion criteria are met

- Diagnosis of primary brain tumor or symptomatic brain metastasis. Patients with brain
metastases must be without neurologic dysfunction that would confound the evaluation
of neurologic and other AEs