Study Evaluating the Efficacy of a Double Immunotherapy Combined With Olaparib in Patients With Solid Cancers and Carriers of Homologous Recombination Repair Genes After Olaparib Treatment

Inclusion Criteria: Inclusion Criteria from STEP 1: 1. Capable of giving signed informed consent 2. Exome sequencing of tumor and constitutive DNA should have been already performed 3. Patients must be diagnosed with a solid malignancy with the following cancer histologically confirmed with specified inclusion for each cohort: Metastatic breast cancer: • In second line • third line and after Metastatic lung cancer: * Non-small cell lung cancer * Must have progressed after at least a first line with platinum based therapy Metastatic head and Neck cancer • Must have progressed after at least a first line with platinum based therapy Metastatic endometrial cancer • Progression after 1 prior systemic, platinum-based chemotherapy regimen for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting. There is no restriction regarding prior hormonal therapy Metastatic clear cell renal cancer • Must have progressed after at least a line with anti-angiogenic agent. Metastatic pancreatic cancer • Must have progressed after at least a line with FOLFIRINOX regimen and/or Gemcitabin based chemotherapy Locally advanced or metastatic ovarian cancer • Must have received at least one and no more than two lines of prior platinum-containing therapy and progressed after the most recent platinum therapy in a platinum-sensitive timeframe (more than 6 months from the last dose of platinum before randomization) Metastatic urothelial cancer • From the second line and regardless previous treatment (except immunotherapy) Metastatic prostate cancer * Documented evidence of metastatic castration resistant prostate cancer (mCRPC) * Ongoing therapy with LHRH analog or bilateral orchiectomy * Must have progressed on prior new hormonal agent (enzalutamine or abiraterone) and taxane chemotherapy 4. Presence of mutation in homologous repair gene 5. Age \>18 years 6. Performance status ECOG of 0 or 1. 7. Life expectancy ≥ 6 months. 8. At least one lesion measurable as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1) 9. Body weight \>30 kg. 10. 10\. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment 11. Postmenopausal or evidence of non-childbearing status for women of childbearing potential 12. Male patients must use a condom during treatment of STEP1 (olaparib) and STEP2 (durvalumab and tremelimumab) and for 180 days after the last dose when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential 13. Patient is willing and able to comply with the protocol for the duration of the study. 14. For all oral medications patients must be able to comfortably swallow capsules; Inclusion criteria STEP 2 16\. CT Scan evaluation after 6 weeks of olaparib should present response or stable disease as defined by RECIST v1.1 criteria. Exclusion Criteria: Exclusion criteria of STEP 1 1. Involvement in the planning and/or conduct of the study 2. Patient with mBRCA1 / 2 that are eligible for current marketing authorization for olaparib (ovarian cancer),and patient eligible for AstraZeneca registration clinical trials, particularly for the prostate cohort 3. Specific exclusion criteria each cohort: Metastatic breast cancer: • Only for patient second line : patient with mBRCA1 / 2 that are eligible for current marketing authorization for Olaparib (ovarian cancer) and patient eligible for AstraZeneca registration clinical trials). Metastatic lung cancer * Small cell cancer * oncogenic addiction : EGFR mutation or BRAF mutation or ALK rearrangement or ROS1 mutation Locally advanced or metastatic ovarian cancer * Patient with mBRCA1 / 2 that are eligible for current marketing authorization for Olaparib (ovarian cancer) and patient eligible for AstraZeneca registration clinical trials. Metastatic prostate cancer • Untreated or first line patients Metastatic head and Neck cancer, Metastatic endometrial cancer, Metastatic clear cell renal cancer, Metastatic pancreatic cancer \& Metastatic urothelial cancer: • None 4. Participation in another clinical study with an investigational product during within 2 months of first administration of Olaparib. 5. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 6. Receipt of the last dose of anticancer therapy ≤21 days prior to the first dose of olaparib or 5 times its half-life, whichever is less. 7. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, ototoxicity, vitiligo, and the laboratory values defined in the inclusion criteria 8. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 9. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. Radiotherapy (non-palliative) within 21 days prior the first dose of study drug or within 6 weeks for therapeutic doses of MIBG or craniospinal irradiation. Palliative RT (which would be \<30% of the bone marrow) to non-target lesions is allowed. 10. Major surgical procedure within 28 days prior to the first dose of olaparib and patients must have recovered from any effects of any major surgery. 11. Patients unable to swallow orally administered medication and patients with Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs 12. History of allogenic organ, bone marrow or double umbilical cord blood transplantation. 13. Active or prior documented autoimmune or inflammatory disorders 14. Uncontrolled intercurrent illness or patient considered a poor medical risk due to a serious, uncontrolled medical disorder, including but not limited to, ongoing or active infection, symptomatic congestive heart failure 15. Currently taking medications with known risk of prolonging the QT interval or inducing Torsades de Pointes. 16. Concomitant use of known strong or moderate CYP3A inducers. 17. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions or patients with congenital long QT syndrome 18. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML. 19. History of another primary malignancy 20. History of leptomeningeal carcinomatosis 21. Patient with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of corticosteroids or local CNS-directed therapy to control their CNS disease. 22. History of active primary immunodeficiency 23. Immunocompromised patients 24. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. Patients with a past or resolved HBV infection are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 25. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. 26. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. 27. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential 28. Prior treatment with any PARP inhibitor including olaparib or immunotherapy. 29. Concomitant use of known strong or moderate cytochrome CYP3A inhibitors and concomitant use of known strong or moderate CYP3A inducers. Exclusion criteria of STEP 2 Patients should not enter the study if any of the exclusion criteria from STEP 1 and the following criteria for STEP 2 are fulfilled: 30. Patient with progression observed on CT scan performed after 6 weeks of olaparib (STEP 1).