Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)

Investigator-assessed Time to Objective Response

Time to objective response is defined as the time from randomization to first response (complete response, CR or partial response, PR). CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference.

Time frame: Randomization to date of first response (approximately 105 months)

Investigator-assessed Time of Progression-free Survival (PFS)

PFS=time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. Participants who die without a reported prior progression and without subsequent anti-cancer therapy were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the date they were randomized. Participants who received any subsequent anti-cancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation date of the subsequent anti-cancer therapy. Progressive disease: \>=20% increase in sum of target lesion diameters and sum must show absolute increase of \>=5mm; smallest sum on study as reference. Based on Kaplan-Meier Estimates.

Time frame: from randomization up to disease progression or death (approximately up to 105 Months)

Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level

Quantifiable PD-L1 expression=percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay. If the PD-L1 staining could not be quantified it was classified as: indeterminate=tumor cell membrane staining hampered for reasons attributed to biology of tumor biopsy specimen and not due to improper sample preparation or handling; not evaluable=tumor biopsy specimen was not optimally collected or prepared. Not evaluable determined from H\&E process before the tumor biopsy specimen was sent for evaluation or from H\&E process during PD-L1 evaluation; baseline PD-L1 expression=if more than one tumor biopsy specimen was available, the most recently collected specimen with a quantifiable result. If all specimens for a given participant are either indeterminate or not evaluable, then the PD-L1 expression was considered indeterminate as long as at least one specimen is indeterminate. Otherwise, PD-L1 expression was considered not evaluable.

Time frame: Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months)

Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events

Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Time frame: Day of first dose to 30 days post study completion (approximately 106 months)

Percentage of Participants With Disease-related Symptom Progression (DRSP)

Disease-related symptom progression rate (DRSPR)=a decrease of two points in the Functional Assessment of Cancer Therapy-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) questionnaire relative to the participant's baseline FKSI-DRS score with no later increase above this threshold observed during the course of the study. The 9 items of the FKSI-DRS were summarized into a symptom scale ranging in score from 0 to 36, with 0 being the worst possible score and 36 being the best possible score. A single measure reporting a decrease of at least 2 units was considered disease-related symptom progression only if it was the last one available for the participant. In order to consider a questionnaire received as valid, over 50% of the items were to be completed. Calculated by the Clopper-Pearson method for each treatment group.

Time frame: from randomization up to disease progression or death (approximately up to 105 Months)

Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests

Aspartate aminotransferase, AST. Alanine aminotransaminase, ALT. Total bilirubin, tBIL. Thyroid stimulating hormone, TSH. Upper limit of normal (ULN). Units per Liter (U/L). Results reported in International System of Units (SI).

Time frame: Day 1 to 30 days post study completion (approximately 106 months)

Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units

Common Terminology Criteria (CTC) version 4.0 in International System of Units (SI); Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Hematology parameters=Hemoglobin (Gr 3: \< 8.0 g/dL), Platelet Count (Gr 3: 25.0 -\< 50.0\*10\^9 c/L; Gr 4: \< 25.0\*10\^9 c/L), Leukocyte Count (Gr 3: 1.0 -\< 2.0\*10\^3 c/µL; Gr4: \< 1.0\*10\^3 c/µL), Absolute Lymphocyte Count (Gr 3: 0.2 -\< 0.5\*10\^3 c/µL; Gr 4: \< 0.2\*10\^3 c/µL), Absolute Neutrophil Count (Gr 3: 0.5 - \< 1.0\*10\^3 c/µL; Gr 4: \< 0.5\*10\^3 c/µL). Liver Function parameters=Alkaline Phosphatase (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), AST (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), ALT (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), tBIL (Gr 3: \> 3.0 - 10.0 mg/dL \* ULN; Gr 4: \> 10.0 mg/dL \* ULN). Renal parameter=Creatinine (Grade: Gr3: \> 3.0 - 6.0 mg/dL \*ULN; Gr4: \> 6.0 mg/dL \*ULN). Cells per microliter (c/µL). Cells per Liter (c/L). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL).

Time frame: Day 1 to 30 days post study completion (approximately 106 months)