Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Randomized, Open-label Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy as a First-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-426)
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) in combination with axitinib versus sunitinib monotherapy as a first-line treatment for participants with advanced/metastatic renal cell carcinoma (mRCC).

The primary hypotheses of this study are:

1. The combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Progression-Free Survival (PFS) as assessed by blinded independent central imaging review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
2. The combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Overall Survival (OS).


Options:
A: Inclusion Criteria:

1. Histologically or cytologically confirmation of renal cell carcinoma with a clear cell histologic component
2. Patients must present with stage IV disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent.
3. Measurable disease according to RECIST criteria are required but patients with evaluable lesions without measurable lesions are allowed to be enrolled to this study
4. ECOG performance status 2 or better
5. Age 18 years or older
6. Adequate bone marrow, hepatic, and renal function
7. Life expectancy of \> 3 months
8. Singed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment

Exclusion Criteria:

1. Known spinal cord compression or carcinomatous meningitis
2. Diagnosis of any serious secondary malignancy within the last 2 years, except for adequately treated basal cell or squamous cell carcinoma of skin, or in situ carcinoma of cervix uteri
3. Hypertension that cannot be controlled by medications (blood pressure \> 150/90 mmHg despite optimal medical therapy)
4. Treatment with anticonvulsant agents and treatment with therapeutic doses of coumadin currently or within 2 weeks prior to first day of sunitinib administration. Low dose coumadin for DVT prophylaxis is permitted (up to 2 mg/day).
5. Pregnancy or breast feeding.
6. Other severe acute or chronic medical or psychiatric condition
7. Prior treatment on sunitinib, sorafenib, or bevacizumab.
B: Inclusion Criteria:

* Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features
* Has locally advanced/metastatic disease (i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer) or has recurrent disease
* Has measurable disease per RECIST 1.1 as assessed by the investigator/site radiologist
* Has received no prior systemic therapy for advanced RCC.
* Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
* Has Karnofsky performance status (KPS) ≥ 70% as assessed within 10 days prior to randomization.
* If receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to randomization.
* Demonstrates adequate organ function.
* Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
* Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria:

* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization.
* Has had major surgery within 4 weeks, received radiation therapy within 2 weeks prior to randomization, or has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to prior treatment.
* Has had prior treatment with any anti-programmed cell death (anti-PD-1), or programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms.
* Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents.
* Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to axitinib or sunitinib.
* Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding physiologic corticosteroid dose or any other form of immunosuppressive therapy within 7 days prior to randomization, except in the case of central nervous system (CNS) metastases.
* Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjøgren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement, are not excluded.
* Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in situ are acceptable if they have undergone potentially curative therapy.
* Has known active CNS metastases and/or carcinomatous meningitis.
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
* Has an active infection requiring systemic therapy.
* Has a known history of Human Immunodeficiency Virus (HIV).
* Has known active Hepatitis B or Hepatitis C infection.
* Has received a live virus vaccine within 30 days of randomization.
* Has a clinically significant gastrointestinal (GI) abnormality including:
* Malabsorption, total gastric resection
* Or any condition that might affect the absorption of orally taken medication
* Active GI bleeding, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
* Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation
* Has QT interval corrected for heart rate (QTc) ≥480 msec.
* Has a history of any of the following cardiovascular conditions within 12 months of randomization:
* Myocardial infarction
* Unstable angina pectoris
* Cardiac angioplasty or stenting
* Coronary/peripheral artery bypass graft
* Class III or IV congestive heart failure per New York Heart Association
* Cerebrovascular accident or transient ischemic attack
* Has a history of deep vein thrombosis or pulmonary embolism within 6 months of screening.
* Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg.
* Has evidence of inadequate wound healing.
* Has active bleeding disorder or other history of significant bleeding episodes within 30 days of randomization.
* Has hemoptysis within 6 weeks prior to randomization.
* Has current use (within 7 days of randomization) or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP3A4/5) inhibitors.
* Has current use (within 7 days of randomization) or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or drugs that are known with proarrhythmic potential.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
* Has had a prior solid organ transplant.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.
C: Inclusion Criteria:

* Patients will be required to have the clear cell variant of renal cell carcinoma with less than 25% of any other histology (including, but not limited to, papillary or chromophobe or oncocytic); there must be histologic confirmation by treating center of either primary or metastatic lesion
* Patients will be required to have measurable metastatic disease that is not curable by standard radiation therapy or surgery; all sites must be assessed within 4 weeks prior to study entry
* Previous nephrectomy is required with the following exceptions:

  * Primary tumor =\< 5 cm, or
  * Extensive liver (\> 30% of liver parenchymal) or multiple (\> 5) bone metastases, making nephrectomy a clinically questionable procedure
  * Unresectable primary tumor due to invasion into adjacent organs or encasing the aorta or vena cava
* No prior cytotoxic chemotherapy; a maximum of one prior regimen of either vaccine or cytokine-based immunotherapy disease is permitted
* No prior anti-angiogenic therapy including, but not limited to, SU11248, ZD6474 or VEGF Trap; no prior therapy with bevacizumab, mammalian target of rapamycin (mTOR) inhibitors (including, but not limited to, temsirolimus), or sorafenib will be allowed; thalidomide or interferon alpha (IFNalpha) are allowed either for adjuvant therapy or stage IV disease
* No immunotherapy within 4 weeks of randomization; toxicities from immunotherapy must have resolved and a minimum of two weeks must pass prior to enrollment
* Prior radiation therapy is permitted, but toxicities from radiation must have resolved and a minimum of 2 weeks must pass prior to randomization
* No history or clinical evidence of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the past 48 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of greater than 12 weeks
* Hemoglobin (Hgb) \>= 9.0 g/dL (transfusions allowed prior to enrollment)
* White blood count (WBC) \>= 3,000/mm\^3
* Absolute granulocyte count (AGC) \>= 1,200/mm\^3
* Platelet count \>= 100,000/mm\^3
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) \>= 55 ml/min
* Total bilirubin =\< 1.5 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN (or =\< 5.0 x ULN in the presence of liver metastases)
* International normalized ratio (INR) =\< 1.5
* Activated partial thromboplastin time (aPTT) within normal limits
* Fasting cholesterol \< 350 mg/dL (9.0 mmol/L)
* Fasting triglycerides \< 400 mg/dL (4.56 mmol/L)
* Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for \>= 5 years prior to the time of randomization
* No history of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to sorafenib, temsirolimus or bevacizumab
* No history of bleeding diathesis or coagulopathy
* Any condition that impairs patient's ability to swallow pills will make patient ineligible
* No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization
* No anticipated need for major surgery during the course of the study
* No current or recent (within 4 weeks of enrollment) use of full-dose of anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting or permanent indwelling IV catheters, for those patients receiving warfarin, INR must be =\< 1.5)
* No clinically significant cardiovascular disease, defined as one of the following:

  * Patients with uncontrolled hypertension (blood pressure \> 150/100 mm/Hg at the time of enrollment); patients with hypertension and blood pressure =\< 150/100 mm/Hg on stable antihypertensive regimen are eligible
  * Myocardial infarction or unstable angina \< 24 weeks prior to registration
  * New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
  * Grade II or greater peripheral vascular disease
* No serious, non-healing wound, ulcer, or bone fracture
* No significant proteinuria at baseline; urine protein must be screened within 2 weeks prior to randomization by urine analysis for urine protein creatinine (UPC) ratio; if UPC ratio is \> 0.5, 24-hour urine protein is to be obtained and the level must be \< 1000 mg for patient enrollment

  * NOTE: UPC ratio of spot urine is an estimation of the 24 urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
* No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 0 or psychiatric illness/social situations that would limit compliance with study requirements
* Patients currently taking any of the following cytochrome P450 enzyme-inducing drugs are ineligible:

  * Phenytoin
  * Carbamazepine
  * Phenobarbital
  * Rifampin
* Pregnant and breastfeeding women are excluded from the study; breastfeeding should be discontinued while receiving therapy; patients must have pregnancy test within 7 days prior to patient randomization if woman is of child-bearing capacity
* Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
D: Inclusion Criteria:

* Histologically and/or cytologically confirmed to have advanced renal cell carcinoma (RCC)
* Majority component of conventional clear-cell type is mandatory
* At least 1 measurable lesion (per RECIST)

Exclusion Criteria:

* Prior systemic treatment for RCC
* Evidence of current or prior central nervous system (CNS) metastases
* Cardiovascular disease
* Pregnant or nursing women
* Additional criteria applies

Answer: B