A Phase II Multicentric Study of Olaparib in PALB2-related Advanced Pancreatic Cancer (PALBOLA)

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• A patient is not eligible for study participation if one of the following criteria is met: - History of other malignant tumors in progress or requiring active treatments except: non-melanomatous skin carcinoma, ductal carcinoma in situ (DCIS); cervical cancer in situ; endometrial cancer G1, stage I; other solid tumors treated curatively without evidence of disease for> = 5 years - Presence of myelodysplastic syndrome / acute myeloid leukemia or suggestive elements for MDS / AML - Presence of symptomatic / uncontrolled CNS disease or presence of carcinomatous meningitis. - Weight loss> 10% during screening and / or decline in PS ECOG to> 1 between the baseline visit and 72 hours prior to the start of therapy - Presence of active infection that requires the initiation of systemic therapy - Presence of psychiatric pathology or substance abuse that may interfere with treatment compliance - Persistent CTCAE toxicity> Grade 2 caused by previous treatments with the exception of alopecia. Patients with CTCAE <= 2 sensorineural neuropathy due to previous oxaliplatin treatments may be included after consultation with the investigator. - Patients considered to be at high risk for uncontrollable medical events (e.g. ventricular arrhythmia, recent myocardial infarction, superior vena cava syndrome ...) - Inability to administer oral therapy or the presence of GI disorders that prevent the absorption of the study drug. - Immunocompromised patients (e.g. HIV) - Active hepatitis (B or C) - Presence of a benign variant or variant of uncertain significance (VUS) of PALB2 - Presence of other histology than ductal adenocarcinoma of the pancreas (e.g. neuroendocrine, adenosquamous, etc.) - Presence of bone disease alone as the site of metastatic disease - Major surgery within two weeks of starting treatment - Previous treatment with PARP inhibitor, including Olaparib - Previous systemic therapy, target therapy or radiotherapy (with the exception of palliation) within 3 weeks of starting the study - Treatment with potent CYP3A inhibitors (see protocol). A 2-week washout period is required - Treatment with potent CYP3A inducers (see protocol). A Version n.1 dated 09/02/2022 5 washout period of 5 weeks for enzalutamide and phenobarbital and 3 weeks for the other agents. - Whole blood transfusion in the last 120. Transfusion of platelets or concentrated red blood cells are allowed (no later than 28 days before the start of treatment) - Receiving allogeneic bone marrow transplant or double umbilical cord blood transplant (dUCBT) - Concomitant participation in another interventional clinical study or within the last 4 weeks - Known hypersensitivity to olaparib or to any of the excipients of the product - ECG indicating uncontrolled cardiac abnormalities or potentially reversible cardiac conditions in the opinion of the investigator - Any condition, therapy or laboratory alteration that may confuse trial data, interfere with trial participation, or make trial participation not the best treatment option for the patient - Involvement in planning / conducting the study - Patient deemed not compliant by the investigator - Patients pregnant woman, in the course of breastfeeding or who are considering a conception (also valid for male patients).