Background: Perioperative chemotherapy is a mainstay in the treatment of locally advanced esophagogastric adenocarcinomas (EGA). Trastuzumab improved survival when added to chemotherapy in pts with HER-2-positive metastatic EGA. We investigated the combination of trastuzumab and FLOT as perioperative treatment in pts with locally advanced EGA. Methods: A multicenter phase II study evaluated the efficacy & toxicity of perioperative HER-FLOT (24-h 5-FU 2,600 mg/m², leucovorin 200mg/m², oxaliplatin 85mg/mg², docetaxel 50 mg/m², trastuzumab 6mg/kg then 4 mg/kg d1, repeated d15 for four cycles pre- and postoperatively followed by 9 cycles of trastuzumab monotherapy 6mg/kg 3-weekly) in pts with HER-2 positive EGA (IHC 3+ or IHC 2+/ ISH+). Pts had to have ≥cT2, any N, M0 EGA. The primary endpoint was the rate of centrally tested pathological complete remissions (pCR). Secondary endpoints comprised disease-free and overall survival, R0 resection rate, toxicity and surgical morbidity. Here we report data of an interim safety analysis conducted in the first n=25 pts as well as surgical and pathological results of the first n=45 pts. Results: n=58 pts with a median age of 62 years were included. n=40 pts had tumors originating from the esophagogastric junction. T stage was: (cT2/3/4/unk) 4/44/9/1. n= 52 pts had cN+ disease. The interim safety analysis of four cycles of preoperative HER-FLOT revealed no unexpected safety findings (adverse events grade 3-4: neutropenia 28%, diarrhea 8%, nausea 8%). Thus far, data on surgery and central pathology of 45 patients are evaluable. R0 resection rate was 93.3%. In five pts anastomotic leakage was diagnosed, and five pts came in need of operative revision. One postoperative death occurred. Regarding the primary endpoint, pCR was found in 10 /45 pts (22.2%) and a further n=11 pts (24.4%) had near complete regression (<10 % residual tumor cells). Conclusions: HER-FLOT was found to be safe and no new or unexpected safety issues were noticed. Preliminary data on centrally assessed pCR rate is very promising with >20% achieving a pCR. Final analysis will be presented at the meeting. Clinical trial information: NCT01472029.