Phase II Study of Pembrolizumab After Curative Intent Treatment for Oligometastatic Non-Small Cell Lung Cancer
Condition: Oligometastatic Non-small Cell Lung Cancer (NSCLC)
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to see how well the experimental drug pembrolizumab
      (MK-3475) works in people with oligometastatic NSCLC who have already had treatment for their
      disease. All patients will receive 200 mg of pembrolizumab intravenously on Day 1 of each
      21-day cycle. Patients will receive the study drug for up to 8 cycles, and then if their
      disease is doing well and the study doctor thinks they will benefit patients may receive
      pembrolizumab for up to 8 more cycles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provide written informed consent for the trial.

          -  18 years of age on day of signing informed consent.

          -  Completion of definitive therapy 4-12 weeks prior to enrollment. There are no specific
             limitations on which treatment modalities can be used in the definitive setting (e.g.
             the use of adjuvant chemotherapy is acceptable), but all other treatments must be
             complete at least 4 weeks prior to enrollment.

          -  Provision of tissue from an archival tissue sample or newly obtained core or
             excisional biopsy of a tumor lesion.

               1. Tumor tissue may be from a diagnostic biopsy or a portion of a surgical specimen,
                  if surgery is a component of definitive intent therapy.

               2. Formalin fixed paraffin embedded (FFPE) tissue samples are acceptable; a fine
                  needle aspirate, frozen sample, plastic embedded sample, cell block, clot, bone,
                  bone marrow or cytologic specimen will not be acceptable for IHC analysis.

               3. It is recommended that FFPE blocks be sectioned fresh (within 7 days of
                  sectioning and sending for PD-L1 analysis) onto positively charged slides; slides
                  should be stored and shipped (and stored upon receipt at Qualtek) at 2-8C in the
                  dark.

               4. Recommended fixation time for samples is 24 hours to 48 hours in 10% neutral
                  buffered formalin.

          -  Performance status of 0 or 1 on the ECOG Performance Scale.

          -  Adequate organ function, all screening labs should be performed within 10 days of
             treatment initiation.

        Absolute neutrophil count

          -  1,250 /mcL Product: Pembrolizumab Protocol/Amendment No.: 09/19/2014 10 (ANC)
             Platelets

          -  100,000 / mcL Hemoglobin

          -  9 g/dL or ≥5.6 mmol/L Renal Serum creatinine OR Measured or calculateda creatinine
             clearance (GFR can also be used in place of creatinine or CrCl)

             ≤1.5 X upper limit of normal (ULN) OR

          -  50 mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic 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 aCreatinine clearance should be
                  calculated per institutional standard.

                    -  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.

                    -  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 duration of the study through 120 days after the last dose
                       of study medication. Subjects of childbearing potential are those who have
                       not been surgically sterilized or have not been free from menses for > 1
                       year.

                    -  Male subjects who are partnered with women of childbearing potential should
                       be willing to use 2 methods of birth control, be surgically sterile or
                       abstain from heterosexual activity for the duration of the study through 120
                       days after the last dose of study medication.

        Exclusion Criteria:

          -  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.

          -  Diagnosis of immunodeficiency or exposure to systemic steroid therapy or any other
             form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment (Nasal or oral inhalers are permissible).

          -  Prior monoclonal antibody within 4 weeks prior to study Day 1 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.

          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
             weeks prior to Day 1 drug administration on study or inability to recover (i.e., ≤
             Grade 1 or at baseline) from adverse events due to a previously administered agent.

          -  Note: Subjects with ≤ Grade 2 neuropathy or alopecia are exceptions to this criterion
             and may qualify for the study.

          -  Note: If subject had major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy.

          -  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

          -  Known untreated central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Active autoimmune 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 are an exception to this rule. Subjects that require
             intermittent use of bronchodilators or local steroid injections are not excluded from
             the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's
             syndrome are not excluded from the study.

          -  Evidence of pre-existing interstitial lung disease or active, non-infectious
             pneumonitis.

          -  Active infection requiring systemic therapy with IV antibiotics

          -  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.

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial.

          -  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.

          -  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).

          -  Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Known active Hepatitis B (e.g., HBsAg positive or HBV DNA detectable) or Hepatitis C
             (e.g., HCV RNA [qualitative] is detected).

          -  Receipt of live vaccine within 30 days prior to the first dose of trial treatment.

          -  Progressive disease or sites of new metastasis after definitive therapy for
             oligometastatic disease.

          -  Completion of definitive therapy for oligometastatic disease greater than 12 weeks
             prior to enrollment.