Epacadostat (INCB24360) in Combination With Sirolimus in Advanced Malignancy

Inclusion Criteria: Participants must meet all of the inclusion criteria to participate in this study. * Ability to understand and the willingness to sign a written informed consent. * Prior treatment with at least one line of systemic therapy. * Dose escalation: subjects with advanced and unresectable solid tumor who progressed on at least one line of systemic therapy, and no approved therapy or standard therapy with demonstrated clinical benefit exists; and all subjects with T790M mutation positive NSCLC have progressed on osimertinib. \*Note - Disease measurability is not required for dose escalation. * Dose expansion: subjects with metastatic or recurrent NSCLC who progressed on at least one line of systemic therapy for metastatic or recurrent disease, which must include anti PD-1 or PD-L1 inhibitor, and must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and accessible tumor for biopsy. Molecular status of Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) must have been assessed for nonsquamous NSCLC. Those with activating EGFR mutation or ALK gene arrangement must have progressed on at least one kinase inhibitor. * Age ≥ 18 years. * Eastern Cooperative Oncology Group (ECOG) Performance Status #0-2. * Adequate organ and marrow function as defined below: * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/microliter (mcL) * Platelets ≥ 100,000/mcL * Hemoglobin ≥ 9 grams per deciliter (g/dL) * Total bilirubin within normal institutional limits * Aspartate Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT) ≤ 2.5 X institutional upper limit of normal (ULN) * Alanine Aminotransferase (ALT) Serum Glutamic Pyruvic Transaminase (SPGT) ≤ 2.5 X ULN * Alkaline Phosphatase Level (ALP) ≤ 2.5 X ULN * Serum creatinine ≤ 1.5 X ULN or Creatinine Clearance (CrCl) ≥ 50ml/min * Note: Subjects with bone metastasis and no liver metastasis on screening image may enroll if ALP is \<5 X ULN. Subjects with liver metastasis may enroll if all of AST/ALT/ALP are \<5 X ULN. However, subjects with extensive liver metastasis occupying more than 50% of liver parenchyma will be excluded. * Activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, as long as partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants. * Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) Exclusion Criteria: Participants meeting any of the exclusion criteria at baseline will be excluded from study participation. * Current or anticipated use of other investigational agents while participating in this study. * Participation in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) before first dose. * Subjects who have received an IDO inhibitor. Subjects who have received other immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, and any other treatment targeting T-cell) will be permitted. Subjects who have received experimental vaccines or other immune therapies should be discussed with the Principal Investigator (PI) to confirm eligibility. * Subjects who have received sirolimus, everolimus, temsirolimus, or any other agent for current malignancy that theoretically targets Phosphoinositide 3-kinase (PI3K), AKT and / or mTOR. * Any prior ≥ Grade 3 immune-related adverse event (irAE) while receiving immunotherapy, including anti-Cytotoxic T-Lymphocyte antigen 4 (CTLA-4) and anti-PD-1/PD-L1 treatment, or any unresolved irAE\>Grade 1. \*Note: Previous immune-related ocular toxicity of any grade is excluded. * Subjects who are receiving an immunosuppressive treatment for any reason, including chronic use of systemic steroid or prednisone equivalent at doses ≥ 10 milligrams per day (mg/day) within 14 days prior to the first dose of study treatment. Use of inhaled or topical steroids or systemic corticosteroids \< 10 mg is permitted. * Subjects who have had prior radiotherapy within 2 weeks of therapy. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. * Patient has received chemotherapy within 3 weeks prior to entering the study or has not recovered sufficiently (i.e., greater than grade 1. PI will judge patient recovery status) from adverse events due to agents administered more than 3 weeks earlier. Exceptions are stable chronic toxicities not expected to resolve, such as peripheral neurotoxicity, alopecia, and fatigue. * Prior monoclonal antibody within 4 weeks before study Day 1 or not recovered (≤ Grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier. Exception to this rule would be use of denosumab. * Brain metastases: Symptomatic, unstable, or disease requiring use of steroid treatment. * Subjects with any active or inactive autoimmune process (eg, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) or who are receiving systemic therapy for an autoimmune or inflammatory disease. \*Exceptions include subjects with vitiligo, hypothyroidism stable on hormone replacement, controlled asthma, Type I diabetes, Graves' disease, Hashimoto's disease, or with PI approval. * Evidence of or any history of interstitial lung disease or active, noninfectious pneumonitis including symptomatic and/or pneumonitis requiring treatment. * Hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or at risk for HBV reactivation. Hepatitis B virus deoxyribonucleic acid (DNA) and testing for HCV ribonucleic acid (RNA) must be undetectable. At risk for HBV reactivation is defined as hepatitis B surface antigen positive * Subjects with clinical condition where subjects may not tolerate immune mediated hepatotoxicity. This includes extensive liver metastasis (See INCLUSION CRITERIA), excessive intake of alcohol (Male \>4 drinks/day, Female \>2 drinks\>day), and the use of acetaminophen \>2 gms/day. Per INCB24360 investigator's brochure. * History or presence of an abnormal ECG which, in the investigator's opinion, is clinically meaningful. Screening corrected QT interval (QTcF) \> 480ms is excluded. Subjects with left bundle branch block are excluded. * History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Current use or anticipated need for treatment with any medications or substances that are inhibitors or inducers of CYP3A4. * Known allergy or reaction to any component of either study drug formulation. Any history of serotonin syndrome (SS) after receiving 1 or more serotonergic drugs. * Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants. * Use of any UDP glucuronosyltransferase family 1 member A9 (UGT1A9) inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid. * Subjects receiving Monoamine Oxidase Inhibitors (MAOIs) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening.