Pembrolizumab With Olaparib as Combined Therapy in Metastatic Pancreatic Cancer

Inclusion Criteria: * Aged ≥ 18 years old * Written informed consent * Histologically or cytologically confirmed PDA * Confirmation that the PDA has TMB \>4 mutations/Mb, or dMMR gene mutation, or MSI-H by IHC. TMB status and dMMR can be obtained from either tissue, or blood. * Radiologically confirmed stage 4 mPDA, with measurable disease * Received no more than 1 prior systemic therapy regimen for unresectable (stage 3 or 4) PDA is allowed * Measurable disease which has not been irradiated in prior radiotherapy * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 * Life expectancy \>12 weeks from the date of screening assessment * Adequate bone marrow function: * Absolute neutrophil count (ANC) ≥1.5 x 109 /L * Haemoglobin (Hb) ≥ 90 g/L * Platelets ≥100 x 109 /L * Adequate liver function: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 x upper limit of normal range (ULN), or \<5 x ULN in the presence of liver metastases * Total bilirubin \<1.5 x ULN * Adequate renal function defined as a calculated creatinine clearance by Cockcroft - Gault of ≥50 mL/min Exclusion Criteria: * Patients with resectable or locally advanced PDA * Other invasive malignancies diagnosed within the last 2 years which have not been treated with curative intent * Prior immune checkpoint inhibitors or PARP inhibitors. This includes any prior therapy with an anti-PD-1, or anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another …