Pembrolizumab and Epacadostat in Patients With Thymic Carcinoma

Exclusion Criteria

• •1. Has disease which is amenable to radical treatment with surgery or radiation or a combination of treatments.
• •2. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• •3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• •4. Has had a prior monoclonal antibody 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.
• •5. 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.
• •* Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• •* Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• •6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• •7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• •8. Has an active automimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• •9. Has evidence of interstitial lung disease
• •10. Has a history of non-infectious pneumonitis that required steroids, or has a history of active pneumonitis.
• •11. Has an active infection requiring systemic therapy.
• •12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •13. Has known hypersensitivity to pembrolizumab (MK-3475) or its formulation.
• •14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •15. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• •16. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• •17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• •18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• •19. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
• •20. Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
• •21. Screening ECG with QTc interval \> 480 milliseconds (corrected by Fridericia). In the event that a single QTc is \>480 msec, the subject may enroll if the average QTc for 3 ECGs is \< 480 msec.
• •22. Prior receipt of an IDO inhibitor.
• •23. Receipt of MAOIs within 21 days before first dose of study treatment.
• •24. History of serotonergic syndrome.