Background: Olaparib (PARP inhibitor) leads to DNA damage and cell death. In phase III study (GOLD), olaparib plus paclitaxel did not improve overall survival (OS) compared with paclitaxel in second-line gastric cancer (GC) patients with statistical significance, even though there was absolute increase of OS (Lancet Oncol 2017). This highlights the importance of biomarker-based patient selection. The changes of tumor microenvironment by paclitaxel/olaparib have not been explored. Besides DNA damage, olaparib induces positive or negative immune modulation by recruiting T cells, promoting type I interferon and upregulating PD-L1, which suggests anti-PD (L1) inhibitor plus olaparib could enhance anti-tumor immunity. Combination of Anti-PD-1 agents with chemotherapy showed a good clinical efficacy in first-line of GC compared with chemotherapy alone (Checkmate 649). Based on these findings, the combination of paclitaxel/olaparib/anti-PD(L1)1 inhibitor, with different mode of actions, might enhance antitumor activity. This is phase II study of paclitaxel/olaparib/durvalumab combination in second-line GC patients, to find out immune modulation effects by paclitaxel/olaparib combination, and to see the efficacy, safety, optimal biomarkers for this combination. Methods: All patients with histologically confirmed unresectable GC have failed to prior one chemotherapy and measurable lesion. Prior exposure to anti-PD(L1)1, PARP inhibitor is excluded. At 1st cycle, paclitaxel (80 mg/m²) on D1, 8 and 15 and olaparib (150 mg bid) on D1-28 is administered. Pre-treatment biopsy and after first cycle biopsy is done. From second cycle, durvalumab 1500 mg on D1 every 4 weeks is added. At the time of disease progression, tumor biopsy is mandatory. Blood samples for biomarkers should be obtained every cycles. Response evaluation is performed after first 3 cycles and repeated every 2 cycles. Primary endpoint is the disease control rate (the percentage of patients who have achieved complete or partial remission, stable disease based on RECIST v1). Key secondary endpoints are overall response rate, progression-free survival, OS, quality of life and safety. Clinical trial information: NCT03579784