Cabozantinib in Combination With Pembrolizumab for the Treatment of Patients With Locally Advanced, Metastatic, or Unresectable Adrenal Cortical Cancer

PRIMARY OBJECTIVE: I. To evaluate the anti-tumor activity of the combination of cabozantinib S-malate (cabozantinib) and pembrolizumab by assessing the overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.). SECONDARY OBJECTIVE: I. To evaluate the efficacy of the combination of cabozantinib and pembrolizumab as measured by progression free survival and overall survival assessed up to 2 years, safety and tolerability of the combination. TERTIARY/EXPLORATORY OBJECTIVE: I. To assess tissue-based assays in archival tissue and correlative changes in peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), blood inflammatory markers and cytokines. OUTLINE: Patients receive cabozantinib orally (PO) once daily (QD) on days 1-21 of each cycle and Pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) at screening and then every 12 weeks on study and undergo collection of blood samples at screening, on study, and at end of treatment. Patients without archival tissue also undergo biopsy at screening. After completion of study treatment, patients are followed for 28 days and then up to 2 years