A Phase I/II Study of Temsirolimus and Sunitinib in Subjects With Advanced Renal Cell Carcinoma

Inclusion Criteria

Inclusion Criteria for Dose Escalation Phase

1. Histologically confirmed advanced RCC.

2. Up to 2 prior systemic regimens for RCC.

3. Subject must have at least 1 measurable lesion that can be accurately measured in at
least 1 dimension with the longest diameter ³10 mm when measured by spiral computed
CT (5-mm slice thickness contiguous) or ³20 mm when measured by conventional CT
(10-mm slice thickness contiguous) (lesion must be ³ 2 times the size of the slice
thickness per RECIST).

- More criteria apply

Exclusion Criteria for Dose Escalation Phase

1. Subjects with known active central nervous system (CNS) malignancy (primary or
metastatic).

2. Prior therapy with sirolimus, temsirolimus or sunitinib.

3. Subjects receiving known strong Cytochrome P450 (CYP)3A4 isoenzyme inhibitors and/or
inducers. Subjects receiving other CYP3A4 isoenzyme inhibitors and/or inducers not
classified as strong inhibitors or inducers are eligible, provided they have been on
a stable regimen for at least 4 weeks before screening.

- More criteria apply

Inclusion Criteria for Expanded Cohort Phase

1. Subjects with histologically confirmed advanced RCC regardless of nephrectomy status
who have received no prior systemic therapies for their disease.

2. Subjects with histologically confirmed advanced RCC regardless of nephrectomy status
who have a least 4 weeks since prior treatment with palliative radiation therapy,
and/or surgery and resolution of all toxic effects of prior therapy to NCI CTCAE
(version 3.0) grade £1.

3. Subjects must have at least 1 measurable lesion that can be accurately measured in at
least 1 dimension with the longest diameter ³10 mm when measured by spiral CT (5-mm
slice thickness contiguous) or ³20 mm when measured by conventional CT (10-mm slice
thickness contiguous) (lesion must be ³2 times the size of the slice thickness per
RECIST).

- More Criteria apply

Exclusion Criteria for the Expanded Cohort Phase

1. Subjects with a history of a CNS malignancy or metastatic disease to the CNS and
subjects with a known, active CNS malignancy (primary or metastatic).

2. Prior anti-vascular endothelial growth factor (anti-VEGF) therapies (with either
monoclonal antibodies and/or tyrosine kinase inhibitors [TKIs]) and/or mTOR
inhibitors.

3. Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers. Subjects
taking other CYP3A4 isoenzyme inhibitors and/or inducers not classified as strong
inhibitors or inducers are eligible, provided they have been on a stable regimen for
at least 4 weeks before screening.

- More Criteria apply