Neoadjuvant Pembrolizumab and Axitinib in Renal Cell Carcinoma With Inferior Vena Cava Tumor Thrombus

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 enrollment.
• •Has had major surgery within 4 weeks or received radiation therapy within 1 week prior to enrollment to the study.
• •Has had prior treatment with any anti-programmed cell death (anti-PD-1) or programmed cell death ligand 1 (PD-L1), 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).
• •Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis) to Axitinib.
• •Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy greater than Prednisone 10 mg daily or a steroid equivalent, or any other form of immunosuppressive therapy within 7 days prior to enrollment to the study except in the case of central nervous system (CNS) metastases.
• •Has an active autoimmune disease requiring systemic treatment within the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjogren'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, thyroid cancer (papillary, hurthle cell or follicular), or localized prostate cancer 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.
• •ALT or AST above 3 times the upper limit of normal
• •Has received a live virus vaccine within 30 days of enrollment to the study.
• •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 enrollment to the study:
• •* 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 poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg on 3 or more dose optimized anti- hypertensive medication.
• •Has evidence of inadequate wound healing per treating physician discretion.
• •Has active bleeding disorder or other history of significant bleeding episodes within 30 days of enrollment to the study.
• •Has current use (within 7 days of enrollment) or anticipated need for treatment with drugs or foods that are known to be strong cytochrome P450 (CYP3A4/5) inhibitors.
• •Has current use (within 7 days of enrollment) 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 by subject self-report.
• •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.