Inclusion Criteria:

          -  Participant must have histologically confirmed malignant pleural mesothelioma that is
             not metastatic or unresectable

          -  Be willing and able to provide written informed consent/assent to the trial.

          -  Be ≥ 18 years of age on day of signing informed consent.

          -  Have measurable disease based on modified RECIST 1.1.

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
             cannot be provided (e.g. inaccessible or subject safety concern) may submit an
             archived specimen only upon agreement from the Investigator Sponsor.

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
             Evaluation of ECOG is to be performed within 7 days prior to the date of
             allocation/randomization.

          -  Demonstrate adequate organ function as defined. If screening hematology and clinical
             chemistry tests are performed within 10 days of Day 1, they need not be repeated at
             Day

          -  Adequate Organ Function Laboratory Values

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Platelets ≥100,000 / mcL

               -  Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (>2 days
                  from assessment)

               -  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

                  ≥60 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

               -  International Normalized Ratio (INR) or Prothrombin Time (PT)-Activated Partial
                  Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant
                  therapy as long as PT or PTT is within therapeutic range of intended use of
                  anticoagulants

                  ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT
                  is within therapeutic range of intended use of anticoagulants

               -  Creatinine clearance should be calculated per institutional standard.

          -  Female subjects 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 negative serum
             pregnancy test will be required.

          -  Female and male subjects of childbearing potential must be willing to use an adequate
             method of contraception

               -  Contraception, for the course of the study through 120 days after the last dose
                  of study medication.

               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred
                  contraception for the subject.

        Exclusion Criteria:

          -  The subject must be excluded from participating in the trial if the subject:

          -  Is currently participating or has participated in a study of an investigational agent
             and received study therapy or used an investigational device within 4 weeks of the
             first dose of treatment.

          -  Has a diagnosis of immunodeficiency including diagnosis of infection with Human
             Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or is receiving systemic steroid
             therapy or any other form of immunosuppressive therapy within 7 days prior to the
             first dose of trial treatment.

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Hypersensitivity to defactinib.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) 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 monoclonal antibody administered more than 4 weeks earlier.

          -  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 treatment.

               -  Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study.

               -  Note: If subject underwent major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include in situ cervical cancer and basal cell carcinoma of the skin or
             squamous cell carcinoma of the skin that has undergone potentially curative therapy.

          -  History of upper gastrointestinal bleeding, ulceration, or perforation within 12
             months prior to the first dose of study drug.

          -  Known history of Gilbert's Syndrome or any current hyperbilirubinemia of any cause.

          -  Known history of stroke or cerebrovascular accident within 6 months prior to the first
             dose of study drug.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis, or has previously treated brain metastases.

          -  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.

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis. Has an active infection requiring systemic therapy.

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  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.

          -  Has 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.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy.

             -- 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 a known history of myocarditis