Study of Pembrolizumab and Cabozantinib in Patients With Metastatic Renal Cell Carcinoma

Inclusion Criteria

• Subjects must have histological or cytological documentation of renal cell carcinoma
• Subjects must have locally advanced, recurrent, or metastatic disease.
• Be willing and able to provide written informed consent/assent for the trial.
• Stated willingness to complywith all study procedures and be available for the duration of the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable or evaluable disease based on RECIST 1.1.
• Recovery to baseline or ≤ Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
• Confirmed availability of representative archival tumor specimens in paraffin blocks (preferred) or ≥ 10 unstained slides, with an associated pathology report.
• Acceptable samples include core needle biopsies for deep tumor tissue or excisional, incisional, or punch biopsies for cutaneous, subcutaneous, or mucosal lesions.
• Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable.
• A subject with insufficient or unavailable archival tissue may be eligible, upon discussion with the Principal Investigator, if the subject is willing to consent to undergo a pretreatment core, punch, or excisional/incisional biopsy sample collection of the tumor.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined by desired lab values.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroiderapy equivalent to ≥ 10 mg/day of prednisone, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Has had prior treatment with pembrolizumab.
• Has had prior treatment with cabozantinib.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Note: Subjects with stable, treated hypothyroidism or adrenal insufficiency may qualify for the study
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Subjects with hypertension managed with medication are an exception to this criterion and may qualify for the study.
• Subjects with ≤ Grade 2 endocrinopathy (e.g. hypothyroidism or adren