Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma

Exclusion Criteria

• •Prior treatment for metastatic disease with \>1 anti-VEGF/VEGFR inhibitor.
• •Prior treatment with anti-PD/PD-L1/CTLA4/IDO antibody (for Cohort B patients only) or ESK981 (for Cohort A and Cohort B patients).
• •Prior mTOR inhibitors or glutaminase inhibitors are allowed.
• •Untreated brain metastases or spinal cord compression.
• •Uncontrolled hypertension defined as blood pressure \>150/90 despite at least 2 anti-hypertensive medication(s) as assessed by 2 blood pressure readings taken at least 1 hour apart during screening.
• •Major surgical procedure or significant traumatic injury within 6 weeks prior to study registration (\> 6 weeks prior to registration is permitted as long as they have fully recovered from any such procedure).
• •History of another primary malignancy except for: malignancy treated with curative intent and no known active disease for ≥2 years, adequately treated non-melanoma skin cancer without current evidence of active disease, adequately treated carcinoma in situ without current evidence of active disease, Gleason ≤6 prostate cancer.
• •Angina, myocardial infarction symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous angioplasty or coronary arterial bypass surgery within the past 3 months.
• •History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g. through surgical resection or repair).
• •The patient has known hypersensitivity to gelatin or lactose monohydrate.
• •The patient has received any investigational drug within 28 days prior to registration or 5 half-lives of the investigational drug, whichever is shorter.
• •History of bleeding disorders (e.g. pulmonary hemorrhage, significant hemoptysis, menometrorrhagia not responding to hormonal treatment) ≤ 6 weeks before Cycle 1 Day1.
• •The patient is on a chronic daily medication known to be a severe or moderate inhibitor or inducer by Micromedex of CYP1A2, CYP2C8, or CYP3A4 at registration.
• •Systemic corticosteroids greater than the equivalent of 10 mg of prednisone or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (such as cyclosporine or methotrexate) and any other medications that could potentially impact the efficacy or safety of the study as judged by the treating investigator are NOT permitted from time of registration to subjects completing protocol therapy unless clinically indicated to manage adverse events or life threatening or serious conditions as determined by the treating investigator.
• •Have any condition that, in the opinion of the investigator, would compromise the ability of the subject to meet or perform study requirements.