Inclusion Criteria:

          1. Signed written informed consent;

          2. Male or female > 18 years of age;

          3. ECOG Performance status (PS) 0-1;

          4. Clinical and histological evidence of OPL with high risk of malignant transformation
             as defined by LOH at 3p14 and/or 9p21 plus at least at one additional chromosomal site
             (4q, 8p,11p,13q, or 17p) or patients with a prior oral cancer history and LOH at 3p14
             and/or 9p21 (LOH defined according to EPOC trial). These conditions define "LOH
             positivity";

          5. OPL with a histological definition of dysplasia and a minimum diameter of at least 20
             mm;

          6. Be willing to provide tissue from newly obtained oral biopsies;

          7. Not receiving chronic systemic steroidal therapy or any immunosuppressive therapy
             within 7 days prior to the first treatment; absence of active autoimmune disease that
             required systemic treatment in the past 2 years, except the following:

               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g.
                  intra-articular injection);

               -  Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or
                  equivalent;

               -  Steroids as premedication for hypersensitivity reactions (e.g. CT scan
                  premedication);

          8. Adequate bone marrow function: neutrophils > 1.5 x 109/L, platelets > 100 x 109/L,
             haemoglobin > 9 g/dL;

          9. Adequate liver function: bilirubin < 2 X upper normal limit (except known medical
             reason not interfering with liver function, such as Gilbert disease), SGOT, SGPT, AP,
             GGT < 3 x ULN;

         10. Adequate renal function: calculated or analysed creatinine clearance > 60 mL/min;

         11. If of childbearing potential, willingness to use effective contraceptive method (Pearl
             Index < 1; e.g. oral contraceptive (pill), hormone spiral, hormone implant,
             transdermal patch, a combination of two barrier methods (condom and diaphragm),
             sterilization, sexual abstinence for the study duration and 2 months post-dosing.

        Exclusion Criteria:

          1. Previous immunotherapy (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or any
             other antibody or drug specifically targeting T-cell co-stimulation or immune
             checkpoint receptors);

          2. Oral lesions due to lichen planus;

          3. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive
             therapy, or known human immunodeficiency virus (HIV) or acquired immunodeficiency
             syndrome (AIDS)-related illness;

          4. Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or
             chronic infection;

          5. Vaccination within 4 weeks of the first dose of avelumab and while on trial is
             prohibited except for the administration of inactivated vaccines (for example,
             inactivated influenza vaccines);

          6. Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart
             Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy,
             uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial
             infarction in the last 12 months;

          7. Significant neurologic or psychiatric disorders including dementia or seizures;

          8. Active uncontrolled infection (requiring IV antibiotics) or active tuberculosis;

          9. Active disseminated intravascular coagulation;

         10. Other serious underlying medical conditions which could impair the ability of the
             patient to participate into the study;

         11. Having participated in another clinical trial or having received any investigational
             agent in the preceding 30 days before study entry;

         12. Known allergic/hypersensitivity reaction to any of the components of the treatment;

         13. Pregnancy (absence confirmed by serum/urine beta HCG) or breastfeeding;

         14. Other active malignancy within 3 years, with the exception of a history of a previous,
             adequately treated:

               -  basal cell carcinoma of the skin

               -  pre-invasive carcinoma of the cervix

               -  superficial bladder cancer

               -  carcinoma in situ of the prostate, cervix or breast,

               -  head and neck squamous cell carcinoma, surgically treated (radiotherapy treatment
                  not allowed);

         15. Legal incapacity or limited legal capacity;

         16. Medical, psychological or socio-geographical condition or situation which in the
             opinion of the investigator would not permit the patient to complete the study or sign
             meaningful informed consent;

         17. Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes
             mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to
             recur in the absence of an external trigger are permitted to be enrolled;

         18. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily
             prednisone equivalents) or other immunosuppressive medications within 7 days of study
             drug administration. Inhaled or topical steroids, steroids as premedication for
             hypersensitivity reactions and adrenal replacement doses > 10 mg daily prednisone
             equivalents are permitted in the absence of active autoimmune disease.