Background: Peri-operative chemotherapy with 5FU, oxaliplatin and docetaxel (FLOT) is a new standard of care in resectable gastro-oesophageal adenocarcinoma (GOA), however with 3y survival rates of only 57% there is a need to further improve outcomes by developing innovative therapeutic combinations. PD1/PDL1 checkpoint inhibitors have shown activity in GOA and we are conducting a single-arm phase II trial to investigate the safety and efficacy of the anti-PDL1 antibody avelumab in combination with FLOT (FLOT-A) as peri-operative therapy in resectable GOA. The combination aims to generate synergy by enhancing progression through the cancer-immunity cycle via the pro-immunogenic effect of FLOT chemotherapy and simultaneous avelumab-induced release of the immune inhibitory effect of the PD1/PDL1 checkpoint. Methods: The 2-stage trial design will evaluate the safety and efficacy of avelumab (starting dose: 10mg/kg IV 2 weekly, pre-planned dose reduction to 7mg/kg IV 2 weekly if dose limiting toxicities occur) with standard dose FLOT chemotherapy (5FU 2600mg/m2/24hr, leucovorin 200mg/m2, oxaliplatin 85mg/m2 and docetaxel 50mg/m2) for pts with operable GOA treated on a peri-operative pathway. Stage 1 will establish the safe and maximum tolerated dose of FLOT-A using a 3+3 dose finding design. Stage 2 will assess the efficacy of FLOT-A based on pathological complete response (pCR) rate and peri-op safety. The primary endpoint is pCR. Using an A’hern single stage design to rule out a lower limit of 10% pCR rate and demonstrate an increase to 25% requires the inclusion of 40 pts, to achieve 80% power and a 1-sided 0.05 significance level. An interim analysis will assess safety and Mandard tumour regression grading (TRG) after 15 pts become evaluable. If ≥5 pts achieve TRG 1-3 the trial will expand to 40 pts. Secondary endpoints are ORR, PFS and OS. Exploratory objectives will investigate dynamic changes of immune infiltrates in baseline and on-treatment biopsies and correlate neoepitope load, blood lymphocyte activation and faecal microbiome with tumour response. Recruitment commenced in July 2017 and 40 pts will be recruited in 2 years. Clinical trial information: NCT03399071