Epacadostat (INCB24360) in Combination With Sirolimus in Advanced Malignancy

• 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)

Participants meeting any of the