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 signedinformed 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 FiltrationRate50 ml/min by Cockroft/Gault formula

11. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkalinephosphatase, 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 nomore than 1 week (7 days) prior to registration, tumour assessment (CT or MRI scan ofthe head and neck, chest, abdomen and pelvis at the discretion of the investigator) nomore 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 forfemale pre-menopausal patients. Women will be considered post-menopausal if they havebeen amenorrheic for 12 months without an alternative medical cause. The followingage-specific requirements apply:

18. Women <50 years of age would be considered post-menopausal if theyhave beenamenorrheic for 12 months or more following cessation of exogenous hormonaltreatments and if they have luteinizing hormone and follicle stimulating hormonelevels in the post-menopausal range for the institution or underwent surgicalsterilization (bilateral oophorectomy or hysterectomy).

19. Women ≥50 years of age would be considered post-menopausal if they have beenamenorrheic for 12 months or more following cessation of all exogenous hormonaltreatments, had radiation-induced menopause with last menses >1 year ago, hadchemotherapy-induced menopause with last menses >1 year ago, or underwentsurgical sterilization (bilateral oophorectomy, bilateral salpingectomy orhysterectomy). For female patients of childbearing potential, negative serumpregnancy test within 1 week (7 days) prior of starting study treatment

20. Women of childbearing potential and their partners, who are sexually active, mustagree 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 (accordingto the treatment group) after last dose of study drug(s) (where applicable). Malepatients 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 hetreatment 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 targetedtherapy, immunotherapy)

4. Treatment with any other investigational medicinal product within 28 days prior tostudy 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 andup to 30 days after the last dose of IMP.

7. Treatment with CYP3A4 inhibitors as well as inducers, unless discontinued 7 days priorto randomization

8. Any of the following within 3 months prior to inclusion: grade 3-4 gastrointestinalbleeding, 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-situcarcinoma 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 traumaticinjury 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 orpulmonary 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, malabsorptionsyndrome, bowel obstruction or inability to take oral medication

17. Active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, orany other disease or condition associated with chronic inflammation.

18. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) orevidence of interstitial lung disease on baseline chest CT scan

19. Other clinically significant disease or co-morbidity which may adversely affect thesafe 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 contraceptivemeasures