An Open-Label, Multicenter, Phase 1b/2 Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment

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Inclusion Criteria:

- Histologically confirmed diagnosis of renal cell carcinoma.

- Phase 2: Histological or cytological confirmation of predominant clear cell RCC
(original tissue diagnosis of RCC is acceptable).

- Documented evidence of unresectable advanced or metastatic RCC. Phase 2: Radiographic
evidence of disease progression according to modified Response Evaluation Criteria in
Solid Tumors (RECIST 1.1).

- Phase 2: One prior vascular endothelial growth factor (VEGF)-targeted treatment (for
example, but not limited to, sunitinib, sorafenib, pazopanib, bevacizumab, axitinib,
vatalanib, AV951/tivozanib) for unresectable advanced or metastatic RCC.

- Phase 2: Measurable disease meeting the following criteria: a.) at least 1 lesion of
greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or
greater than or equal to 1.5 cm in the short axis diameter for a lymph node which is
serially measurable according to Modified RECIST 1.1 using computerized
tomography/magnetic resonance imaging (CT/MRI) or photography. Subjects must have an
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

- Adequately controlled blood pressure (BP) with or without antihypertensive
medications, defined as BP less than or equal to 150/90 mmHg at screening and no
change in antihypertensive medications within 1 week prior to the Screening Visit.

Select Exclusion Criteria:

Phase 1b or Phase 2 specific per below:

- Phase 1b only: Subjects with untreated or unstable metastasis to the central nervous
system (CNS) are excluded. Subjects who have completed local therapy and have
discontinued the use of steroids for this indication at least 4 weeks prior to
commencing treatment and in whom stability has been proven by at least 2 CT or MRI
scans obtained at least 4 weeks apart are eligible for Phase 1b only. Phase 2 only:
Subjects with CNS (e.g., brain or leptomeningeal) metastasis are excluded.

- Phase 2 only: More than one prior VEGF-targeted treatment for unresectable advanced
or metastatic RCC.

Phase 1b or Phase 2 specific per below:

- Phase 1b only: Prior exposure to E7080. Phase 2 only: Prior exposure to E7080 or
mammalian target of rapamycin (mTOR) inhibitor.

- Subjects should not have received any anti-cancer treatment within 21 days or any
investigational agent within 30 days prior to the first dose of study drug and should
have recovered from any toxicity related to previous anti-cancer treatment. Major
surgery within 3 weeks prior to the first dose of study drug.

- Subjects having > 1+ proteinuria on urinalysis will undergo 24-hour urine collection
for quantitative assessment of proteinuria.

- Subjects with urine protein greater than or equal to 1 g/24-hour will be ineligible.
Uncontrolled diabetes as defined by fasting serum glucose >1.5 X ULN.

- Phase 2 only: Active malignancy (except for renal cell carcinoma, melanoma in-situ,
basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix)
within the past 24 months.

- Known intolerance to any of the study drugs (or any of the excipients) and/or known
hypersensitivity to rapamycins (e.g., sirolimus, everolimus, temsirolimus) or any of
the excipients.

- Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to
toxicity will be ineligible.