MLN0128 and MLN0128 + MLN1117 Compared With Everolimus in the Treatment of Adults With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma

Inclusion Criteria

• Male or female participants aged 18 years or older.
• Histologically confirmed renal cell carcinoma (RCC) with a clear-cell component.
• Evidence that the RCC is advanced or metastatic.
• Radiologic evidence of PD (according to RECIST Version 1.1) either during or within 6 months after stopping their most recent systemic therapy for RCC before enrollment into this study.
• At least 1, prior line of VEGF-targeted therapy, but not more than 4 total prior lines of systemic therapy. Exposure to more than 1 line of VEGF-targeted therapy is acceptable. Participants may also have received prior therapies with interferon, interleukin 2 (IL-2), anti-PD1 antibodies, cabozantinib or other experimental agents, but not prior therapy with any agent that targets phosphoinositide 3-kinase (PI3K), serine/ threonine-specific protein kinase (AKT), or mechanistic (or mammalian) target of rapamycin (mTOR).
• Karnofsky Performance Status (KPS) greater than or equal to (>=) 70%.
• Life expectancy of >=3 months.
• Female participants who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 1 highly effective method of contraception, and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labelling [example, United States Prescribing Information (USPI), Summary of Product Characteristics (SmPC), etc;]) after the last dose of study drug, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.).

Male participants, even if surgically sterilized (that is, status postvasectomy), who:

• Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug (or longer, as mandated by local labelling [example, USPI, SmPC, etc]), OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods for the female partner], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.).
• Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug.
• Suitable venous access for the study-required blood sampling.
• Screening clinical laboratory values:
• Absolute neutrophil count >=2000 per microliter (/mcL) and platelet count >=100,000/mcL;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to ( =40 milliliter per minute (mL/min) / 1.73 square meter (m^2);
• Glycosylated hemoglobin (HbA1c) less than ( ] 160 millimeter of mercury [mm Hg]; diastolic blood pressure >95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle 1 Day 1 is allowed;
• Pulmonary hypertension.
• Uncontrolled asthma or oxygen saturation 480 millisecond [ms], or history of congenital, long-QT syndrome, or torsades de pointes).
• Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer, superficial bladder cancer, very low risk prostate on observation, or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Prior therapy with agents that target Phosphatidylinositide 3-kinases (PI3K), Protein