Primary Objective(s), Hypothesis(es), and Endpoint(s):~(1) Objective: Assess the clinical efficacy of the combined use of MT with PEM in patients with advanced ACC.~Hypothesis: We hypothesize that adding PEM will enhance the clinical efficacy of MT. This additive/synergistic effect could be related to the intrinsic adrenolytic activity of MT that could lead to antigens exposures to immune cells. Furthermore, the cortisol lowering effect of mitotane is expected to alter the tumor microenvironment leading to a change the milieu of the tumor infiltrating immune cells to make ACC more susceptible to PEM. Also, cortisol lowering can reduce lymphocytes inhibition and enhances the efficacy of PEM.~Primary Endpoint: Overall response rate (ORR) assessed objectively using RECIST 1.1 criteria defined as the percentage of patients who have a partial or complete response to the combined treatment of MT plus PEM~Secondary Objective(s), Hypothesis(es), and Endpoint(s):~(1) Objective: Evaluate the safety and efficacy of the combined use of MT plus PEM in patients with advanced ACC.~Hypothesis: The optimal MT plasma levels have not been established prospectively in metastatic ACC. We hypothesize that mitotane level of 14-20 mg/L is associated with oncological responses, but we also anticipate that the combined use of PEM MT could be associated with responses at lower levels of MT which might be associated with more favorable AE profile of MT.~Secondary Endpoints:~Overall survival (OS), defined as the time from combination therapy to death from any cause.~Progression Free Survival (PFS), defined as the time from the start of combination therapy phase to disease progression or death from any cause.~Explore the association between MT level and response to therapy~Safety assessment by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0~Exploratory Objective(s):~(1) Objective: Correlate safety and efficacy data with steroid profile, immune markers and MT levels.~Obtain optional tumor biopsy prior to, during, and after treatment with MT/PEM combination to study immune markers such as infiltrating tumor lymphocytes, and other immune markers during therapy.~Study the changes in circulating markers (MT level, immune cytokines, steroid profile) in blood samples obtained prior to, during, and after treatment with MT/PEM combination
To learn if adding pembrolizumab to mitotane can help to control ACC. The safety of this drug combination will also be studied.