Inclusion Criteria:

        All Patients:

          -  Informed, written consent

          -  Male or female, aged 18 years or older at the time consent is given

          -  ECOG performance status 0 or 1, with no deterioration over the previous 2 weeks

          -  Life expectancy of at least 3 months

          -  Measurable disease according to irRECIST criteria, with at least one measurable lesion
             that has objectively progressed since (or on) any previous therapy

          -  Adequate bone marrow, liver and renal function on blood investigations within 7 days
             prior to treatment initiation

          -  Patients must have been offered all appropriate standard-of-care treatments (or all
             those indicated before anti-PD-1/PD-L1 therapy, if licensed)

          -  Patients must agree to use adequate contraceptive measures for the course of the study
             through 120 days after the last dose of study medication

          -  Women of child-bearing potential must have a negative pregnancy test within 72 hours
             prior to start of dosing

          -  Consent to supply any available archival tissue

        Dose escalation (Phase I):

          -  Pathological diagnosis of any advanced solid tumour type, with confirmation that a
             tissue sample (core biopsy or resected specimen) is available

        Pancreatic expansion (Phase IIa):

          -  Pathological diagnosis of pancreatic ductal adenocarcinoma with confirmation that a
             tissue sample (core biopsy or resected specimen) is available

        NSCLC expansion (Phase IIa):

          -  Pathological diagnosis of non-small cell lung cancer (NSCLC)

          -  Lesion suitable for repeat biopsy

          -  Baseline biopsy containing tumour material during eligibility

          -  Consent for paired biopsies on study

        Mesothelioma expansion (Phase IIa):

          -  Pathological diagnosis of mesothelioma

          -  Lesion suitable for repeat biopsy

          -  Baseline biopsy containing tumour material during eligibility

          -  Consent for paired biopsies on study

        Exclusion Criteria:

        All patients:

          -  An additional invasive cancer in the last 5 years (other than treated and controlled
             localised non-melanoma skin cancer or cervical carcinoma-in-situ, or indolent prostate
             cancer that has been stable for > 1 year)

          -  Any central nervous system metastases unless treated and asymptomatic, as well as
             stable on imaging and not requiring steroids in the preceding 4 weeks

          -  Any interventional studies, systemic cancer therapies or monoclonal antibodies in the
             preceding 4 weeks (6 weeks for mitomycin C and nitrosureas)

          -  Any live vaccines in the preceding 4 weeks

          -  Systemic immunosuppressive agents in the preceding 2 weeks. Immunosuppressive agents
             include steroids such as prednisolone (doses ≥ 15 mg daily) or dexamethasone (doses ≥
             2 mg daily).

        Replacement therapy (e.g. physiologic corticosteroid replacement therapy for adrenal or
        pituitary insufficiency etc) is not considered a form of systemic treatment

          -  Diagnosis of immunodeficiency

          -  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

          -  Known interstitial lung disease or active, non-infectious pneumonitis

          -  Known history of Tuberculosis (TB), Human Immunodeficiency Virus (HIV) or active
             Hepatitis B or C

          -  Other severe or uncontrolled systemic diseases (e.g. uncontrolled hypertension, recent
             myocardial infarction, organ failure or active infection)

          -  Residual (non-laboratory) toxicities greater than grade 1 (CTCAE v4.03) from previous
             therapies despite optimal supportive therapy, including fatigue, anorexia, nausea or
             diarrhoea, but with the exception of alopecia

          -  Pregnancy or lactation

          -  Limited ability to swallow or absorb oral medications

          -  Hypersensitivity to defactinib (VS-6063), pembrolizumab or excipients (including
             L-histidine, L-histidine hydrochloride monohydrate, sucrose or polysorbate 80)

          -  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 is not in the best interest of the
             subject to participate, in the opinion of the treating investigator

          -  Previous treatment with an anti-PD-1 or anti-PDL1 agent

          -  Previous severe or life-threatening skin adverse reaction with other
             immune-stimulatory anticancer agents

          -  Current solid organ transplant recipient