Dose Escalation Study of MLN0128 in Subjects With Advanced Malignancies

Inclusion Criteria:

• Voluntary written consent
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Ability to swallow oral medications
• Life expectancy of ≥6 months
• For women of child-bearing potential, negative serum or urine 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 30 days following the last study drug administration
• 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
• Clinical laboratory values as specified in the protocol

Additionally, to be eligible for the Dose Expansion portion of the study:

• Subjects must have a pathologic diagnosis of advanced or recurrent endometrial adenocarcinoma with histology demonstrating an endometrioid component, and must have failed at least 1 prior line of standard chemotherapy
• Subjects must have a pathologic diagnosis of advanced/metastatic urothelial cancer (carcinoma of the bladder, ureter, and/or renal pelvis) and must have failed at least 1 line of prior therapy in the metastatic/unresectable setting
• Subjects must have a pathologic diagnosis of advanced renal cell carcinoma (RCC), with histological or cytological confirmation of RCC with a clear cell component, and must have failed at least 1 prior line of anti-VEGF therapy (including but not limited to sunitinib, and/or sorafenib, and/or bevacizumab) and must not have received prior therapy with a TORC1 inhibitor (such as temsirolimus or everolimus); Subjects must have progressed on VEGF-directed therapy within 6 months
• Subjects must have a pathologic diagnosis of advanced renal cell carcinoma (RCC) and must have failed previous treatment with a TORC1 inhibitor (such as temsirolimus or everolimus). Additional nonTORC1-directed prior therapies are allowed if subjects have demonstrated progression on prior TORC1 inhibitor therapy within 6 months.

Exclusion Criteria:

• Diagnosis of primary brain tumor
• Have received prior cancer or other investigational therapy within 2 weeks prior to the first administration of study drug
• Known impaired cardiac function or clinically significant cardiac disease
• Known treatment with systemic corticosteroid within one week prior to the first administration of study drug
• Diabetes mellitus
• HIV infection
• Known active cardiovascular disease condition as specified in protocol
• Failed to recover from the reversible effects of prior anticancer therapies
• Pregnancy (positive serum or urine pregnancy test) or breast feeding
• Malabsorption due to prior gastrointestinal (GI) surgery, GI disease
• Other clinically significant co-morbidities

Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons