Pembrolizumab and Epacadostat in Patients With Thymic Carcinoma
Condition: Thymic Carcinoma; Thymus Neoplasms; Thymus Cancer
MeSH terms: Carcinoma; Thymoma; Thymus Neoplasms
Intervention: Pembrolizumab; Epacadostat
Intervention description: Administration of 200 mg MK-3475 once every 3 weeks; 100mg taken by mouth twice daily
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pembrolizumab; Epacadostat

Summary:

      This is a non-randomized clinical trial in patients with thymic carcinomas who failed prior
      systemic therapy. All subjects will receive pembrolizumab and epacadostat treatment in three
      week cycles until unacceptable toxicity, death, progressive disease or withdrawal.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologic confirmation of thymic carcinoma (WHO Classification, See Appendix 12.1)

          2. Advanced disease (Masaoka staging, See Appendix 12.2) not amenable to curative
             treatment.

          3. At least 1 prior line of chemotherapy.

          4. Progression of disease must be documented prior to study entry.

          5. Absence of any autoimmune syndrome typically associated with thymomas but not thymic
             carcinomas (myasthenia gravis, pure red cell aplasia, etc.).

          6. Be willing and able to provide written informed consent/assent for the trial.

          7. Be at least 18 years of age on day of signing informed consent.

          8. Have measurable disease based on RECIST 1.1.

          9. Have provided tissue from an archival tissue sample or newly obtained core or
             excisional biopsy of a tumor lesion.

         10. Have a performance status of 0 or 1 on the ECOG Performance Scale (See Appendix 12.3).

         11. Demonstrate adequate organ function

         12. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

         13. Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication (Reference
             Section 5.7.2). Subjects of childbearing potential are those who have not been
             surgically sterilized or have not been free from menses for > 1 year.

         14. Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy.

        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.