Phase Ib and Phase II Studies of MK-3475 in Combination + for Renal Cell Carcinoma:

Inclusion Criteria

• Male or female ≥ 18 years of age at time of consent.
• Phase Ib dose escalation cohort study: subjects with histologically assessed metastatic clear cell RCC (defined as more than 50% clear cell component) after failure of at least one systemic therapy for metastatic disease (including, but not limited to prior therapy with interleukin 2, interferon, bevacizumab, VEGF TKI, and mTOR) for metastatic disease. NOTE: A biopsy to prove metastatic disease is not required.
• Phase II study: subjects with treatment-naïve histologically assessed metastatic clear cell RCC (defined as more than 50% clear cell component) and who are candidates for standard first-line therapy. NOTE: A biopsy to prove metastatic disease is not required.
• Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, and obtained by imaging within 28 days prior to registration for protocol therapy.
• Karnofsky Performance Status ≥ 70% within 28 days prior to registration for protocol therapy.
• Life expectancy of 6 months or greater as determined by the treating physician.
• Adequate hepatic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
• total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN
• and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
• and alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
• Adequate renal function within 28 days prior to registration for protocol therapy defined by either of the following criteria:
• serum creatinine ≤ 3 mg/dL
• OR if serum creatinine > 3 mg/dL, estimated glomerular filtration rate (GFR) ≥ 20 mL/min
• Adequate hematologic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
• hemoglobin ≥ 9 g/dL
• and absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L
• and platelet count ≥ 100 × 10^9/L
• Adequate coagulation functioning within 28 days prior to registration for protocol therapy defined by either of the following criteria:
• INR ½ teaspoon of blood)
• Pre-existing bleeding diathesis, coagulopathy or hemorrhage
• Myocardial infarction or cerebrovascular accident within 6 months prior to study registration
• Any drugs or supplements that interfere with blood clotting can raise the risk of bleeding during treatment with bevacizumab. These drugs include vitamin E, non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn), warfarin (Coumadin), ticlopidine (Ticlid), and clopidogrel (Plavix).These agents should be used with caution.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for enrollment in this study.
• Presence of any non-healing wound, fracture, or ulcer within 28 days prior to study registration.
• Any condition that, in the opinion of the investigator, might jeopardize the safety of the subject or interfere with protocol compliance.
• Any mental or medical condition that prevents the subject from giving informed consent or participating in the trial.
• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason ≤ grade 7 prostate cancers, or other cancer for which the subject has been disease-free for at least 5 years.
• Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibod