Neoadjuvant Pembrolizumab
Condition: Non-small Cell Lung Carcinoma
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab
Intervention description: Pembrolizumab (prior to surgery) 200 mg IV over 30 min, days 1 & 22, two cycles; followed by surgery; followed by standard adjuvant chemotherapy (per med. oncologist) +/- radiation therapy per institutional standard of care; followed by adjuvant pembrolizumab 200 mg IV over 30 min every 21 days for 4 cycles
-Note: Standard radiation therapy in selected patients for standard clinical indications
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pembrolizumab; Neoadjuvant; Tumor Infiltrating Lymphocytes (TILs)

Summary:

      This multi-institutional, phase 2 clinical trial is studying two doses of pembrolizumab
      administered prior to surgery (neoadjuvant therapy) and 4 doses administered after surgery
      (adjuvant therapy) for stage IB, II or IIIA non-small cell lung cancer. Pembrolizumab is a
      type of immunotherapy that may enhance the ability of the immune system to fight off cancer.
      The study will investigate the effects of pembrolizumab on the immune system and how certain
      immune cells, called TILs (tumor infiltrating lymphocytes), respond to pembrolizumab.
      Previous studies suggest that pembrolizumab could alter the immune cells in a way that the
      the immune cells identify cancer cells. Pembrolizumab has been approved for the treatment of
      advanced lung cancer, but is investigational in this setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed NSCLC.

          -  Clinical stage IB (>/= 3 cm per CT), Stage IIA/IIB, or Stage IIIA (N0-2) amenable to
             surgical resection.

          -  Primary tumor >/= 3 cm (for all stages entered) to make it likely that excess tumor
             will be available after resection.

          -  Patient must be deemed a surgical candidate.

          -  ECOG performance status of 0 or 1 (Appendix C).

          -  No prior chemotherapy, radiation therapy or biologic/targeted therapy for current
             diagnosis of lung cancer.

          -  Adequate Organ Function

          -  Age ≥18 years.

          -  Non-pregnant. Females of child-bearing potential (not surgically sterilized or
             postmenopausal [a woman who is > 45 years of age and has not had menses for greater
             than 1 year]) must test negative for pregnancy within 48 hours prior to any initial
             study procedure based on a serum pregnancy test.

          -  No active invasive malignancy in the past 2 years other than non-melanoma skin cancer.
             Cancers that are in-situ are not considered invasive.

          -  Signed written informed consent including HIPAA according to institutional guidelines.

          -  Patients must agree to research blood sampling to participate in study.

          -  Have measurable disease based on RECIST 1.1.

          -  Post-op predicted FEV1 and DLCO > 40% predicted (or per institutional standard).

        Exclusion Criteria:

          -  Treatment within the last 30 days with a drug that has not received regulatory
             approval for any indication at the time of study entry or used an investigational
             device within 4 weeks of the first dose of treatment.

          -  Has a known history of active TB (Bacillus Tuberculosis).

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Concurrent administration of any other anti-tumor therapy.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L-1, or anti-PD-L2 agent.

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Inability to comply with protocol or study procedures.

          -  Active infection requiring antibiotics, antifungal or antiviral agents, that in the
             opinion of the investigator would compromise the patient's ability to tolerate
             therapy.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency etc) is not considered a
             form of systemic treatment. Patients with a history of inflammatory bowel disease,
             including ulcerative colitis and Crohn's Disease, are excluded from this study, as are
             patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
             progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
             vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune
             origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).

          -  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.

          -  Has a known additional invasive malignancy that is progressing or requires active
             treatment. Exceptions include basal cell carcinoma of the skin or squamous cell
             carcinoma of the skin that has undergone potentially curative therapy or in situ
             cervical cancer.

          -  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.

          -  Has had major surgery (other than definitive lung cancer surgery) within two weeks of
             study or other serious concomitant disorders that in the opinion of the investigator
             would compromise the safety of the patient or compromise the patient's ability to
             complete the study.

          -  Has received any non-oncology vaccine therapy used for prevention of infectious
             diseases (for up to 30 days before or after any dose of pembrolizumab). Note: Seasonal
             influenza vaccines for injection are generally inactivated flu vaccines and are
             allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated
             vaccines and are not allowed.

          -  Has history of myocardial infarction having occurred less than 6 months before
             inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active
             ischemia, or cardiac failure not controlled by medications. Patients with CAD recently
             treated with surgery and/or stent, if stable without symptomatic angina pectoris,
             active ischemia are eligible.

          -  Has a history of interstitial lung disease

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Prisoners or subjects who are compulsorily detained involuntarily incarcerated) for
             treatment of either psychiatric or physical (e.g., infectious) illness.