Preoperative Administration of Olaparib With Cisplatin or With Durvalumab or Alone or no Tratment in Patients Who Are Candidates for Surgery of Carcinoma of the Head and Neck.

Inclusion Criteria:

1. Provision of signed written informed consent prior to any study specific procedures
2. Female and/or male patients aged 18 years and over
3. Body weight higher than 30 Kg
4. Newly diagnosed histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx
5. Provision of biological material (tumor tissue and blood), provision of signed informed consent for translational research
6. Patients selected for a primary surgical treatment
7. No prior anti-cancer treatment for head and neck cancer
8. Performance status ECOG 0-1
9. Adequate hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥10g/dL
10. Adequate renal function: serum creatinine level 1.5 mg/dl and Glomelular Filtration Rate50 ml/min by Cockroft/Gault formula
11. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase, AST (SGOT), ALT (SGPT) 5xULN
12. No active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
13. Ability to swallow tablets.
14. Regular follow-up feasible
15. Baseline evaluations performed before registration: clinical and blood evaluations no more than 1 week (7 days) prior to registration, tumour assessment (CT or MRI scan of the head and neck, chest, abdomen and pelvis at the discretion of the investigator) no more than 30 days prior to registration
16. Treatment initiation planned less than 1 week (7 days) after registration
17. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

    1. Women \<50 years of age would be considered post-menopausal if theyhave been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
    2. Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment
18. Women of childbearing potential and their partners, who are sexually active, must agree to the use of TWO highly effective forms of contraception in combination, throughout the period of taking study treatment and for at least 1-6 month (according to the treatment group) after last dose of study drug(s) (where applicable). Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of TWO highly effective forms of contraception in combination, throughout the period of taking study treatment and for 3- 6 months (according tot he treatment group) after last dose of study drug(s) (where applicable).

Exclusion Criteria:

1. Metastatic or locally advanced unresectable disease
2. Uncontrolled hypercalcemia
3. Concomitant unplanned antitumour therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy)
4. Treatment with any other investigational medicinal product within 28 days prior to study entry
5. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
6. Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP.
7. Treatment with CYP3A4 inhibitors as well as inducers, unless discontinued 7 days prior to randomization
8. Any of the following within 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis
9. Other concomitant or previous malignancy, except: i) adequately treated in-situ carcinoma of the uterine cervix, ii) basal or squamous cell carcinoma of the skin, iii) cancer in complete remission for 5 years
10. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
11. Pregnant or breastfeeding women
12. Patients with known allergy to any excipients to study drugs
13. History of myocardial infarction and/or stroke or other arterialthrombotic events or pulmonary embolism or unstable angina pectoris within 6 months prior to registration
14. No features suggestive of myelodysplastic syndrome/ acute myeloid leukemia MDS/ AML
15. Poorly controlled cardiac arrhythmias
16. Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, bowel obstruction or inability to take oral medication
17. Active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
18. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
19. Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial
20. Known history of positive tests for human immunodeficiency virus (HIV) infection, hepatitis A or C virus, acute or chronic active hepatitis B infection
21. History of severe tumour bleeding or bleeding disorders
22. No blood transfusion within the 28 days prior to study
23. Poorly controlled anti-coagulation therapy (INR3.0 on coumadin or heparin compounds)
24. Palliative radiation therapy within 4 weeks prior to registration
25. Pregnancy or men or women of reproductive age not agreeing to use contraceptive measures