Pembrolizumab and Itacitinib (INCB039110) for Non-Small Cell Lung Cancer
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Itacitinib; Pembrolizumab
Intervention description: a JAK 1 selective small molecule inhibitor; a highly selective humanized monoclonal antibody (mAb)
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a single center, single arm phase 2 study to establish the safety and efficacy of
      itacitinib (also known as INCB039110) administered in combination with pembrolizumab in
      patients with metastatic PD-L1 positive non-small cell lung cancer (NSCLC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. Stage IV or metastatic non-small cell lung cancer (NSCLC)

          -  2. Provide written informed consent for the trial.

          -  3. Patients ≥ 18 years of age

          -  4. Tumor PD-L1≥ 50% as assessed by the PD-L1 IHC 22C3 pharmDx assay (Dako North
             America).

          -  5. Subject must have adequate tumor burden at a safely accessible site for biopsy.
             NOTE: If sites chosen for biopsy were previously irradiated, there must be evidence of
             tumor growth/viable tumor as assessed by the investigator.

          -  6. At least one measurable lesion according to Response Evaluation Criteria in Solid
             Tumors (RECIST) v1.1

          -  7. ECOG performance status 0 or 1

          -  8. Adequate Organ Function Laboratory Values: Absolute neutrophil count (ANC)
             ≥1,250/mcL; Platelets ≥100,000/mcL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L; Serum
             creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine
             clearance (GFR can also be used in place of creatinine or CrCl) ≥50 mL/min for subject
             with creatinine levels > 1.5 X institutional ULN; Serum total bilirubin ≤ 1.5 X ULN OR
             Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN; AST (SGOT)
             and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases

          -  9. Subjects of reproductive potential must agree to use acceptable birth control
             methods.

        Exclusion Criteria:

          -  1. Sensitizing mutations in Epidermal growth factor receptor (EGFR) or anaplastic
             lymphoma kinase (ALK) or ROS1 proto-oncogene receptor tyrosine kinase (ROS1)
             translocations

          -  2. Currently participating in or has participated in a study of an investigational
             agent or anticipated use of an investigational device within 4 weeks of the first dose
             of study treatment.

          -  3. Untreated symptomatic central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  4. Received prior systemic cytotoxic chemotherapy, biologic therapy, targeted therapy
             or immunotherapy for incurable (metastatic) NSCLC.

          -  5. Diagnosis of immunodeficiencywithin 7 days prior to eligibility confirmation by the
             physician-investigator.

          -  6. Prior monoclonal antibodies used for the treatment of NSCLC within 4 weeks prior to
             eligibility confirmation by the physician-investigator, or individuals who have not
             recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  7. Known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, non-invasive bladder tumors, or in situ cervical cancer

          -  8. 8. Active autoimmune disease requiring systemic immunosuppressive treatment within
             the past 3 months prior to eligibility confirmation by the physician-investigator.
             Subjects that require intermittent use of steroid-containing bronchodilators or local
             steroid injections or topical steroid medications are not excluded from the study.
             Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome are
             not excluded from the study.

          -  9. Interstitial lung disease or history of pneumonitis that has required oral or IV
             steroids

          -  10. Active infection requiring systemic therapy with IV antibiotics

          -  11. 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.

          -  12. Known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  13. Pregnant or breastfeeding women

          -  14. 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).

          -  15. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  16. Known active Hepatitis B (e.g., HBsAg positive or HBV DNA detectable) or Hepatitis
             C (e.g., HCV RNA [qualitative] is detected).

          -  17. Anticipated receipt of any live vaccine within 30 days prior to the first dose of
             trial treatment.

        Note: For the purposes of determining eligibility above, enrollment is defined as the date
        of subject consent.