Background: Surgical rection is the only potentially curative intervention for locally advanced adenocarcinoma of esophagus, GEJ and stomach. Results from various studies have demonstrated the benefits of perioperative treatment including neoadjuvant and adjuvant chemotherapy or chemoradiation, however, there is lack of universally accepted standard. Recent data demonstrated the benefit of immune checkpoint inhibitor in adjuvant setting in patients who had pre-operative chemoradiation. This single arm phase 2 trial is aimed to evaluate efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in combination with mFOLFOX in patients with potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach with the primary objectives of pathological response rate (ypRR with tumor regression score, TRS ≤ 2). We are reporting the preliminary analyses while the study nears completion. Methods: Patients with newly diagnosed locally advanced (T1N1-3M0 or T2-3NanyM0), potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach by PET, EUS, CT C/A/P and staging laparoscopy were treated with pre-operative mFOLFOX6 (oxaliplatin 85mg/m², Leucovorin 400mg/m², 5-FU bolus 400mg/m², and 5-FU 2400mg/m² infusion every 2 weeks) for 4 cycles and pembrolizumab (200 mg IV q3week) for 3 cycles. Patients with no evidence of metastatic disease by PET and CT C/A/P who are eligible for resection underwent surgery. Post-operative treatment consisted of 4 cycles of mFOLFOX and 13 cycles of pembrolizumab 4-8 weeks postoperatively. Results: Of 35 patients enrolled (age range 44-86, mean of 65 years; with male:female of 28:7), 33 finished preoperative treatment, 26 had curative intended operations with R0 resection for all, 1 is pending for surgery, and 2 are still on pre-operative treatment. 5 of 26 pts achieved ypCR (19% regression score of 0). All except 2 patients (24/26, 92%) had shown pathologic response to the treatment with TRS ≤ 2. 23/26 (88%) finished post-operative treatment. 20 patients completed all planned treatment with an average follow-up of 22.7 months. Amount them, 2 patients had recurrence/ metastatic disease (at 9 and 10 months, respectively) with 1 died 23.3 months from enrollment, and the rest are all free of disease. G3/4 toxicities were reported in 19 of all 35 treated patients. There were no unexpected toxicities. Conclusions: The combination of FOLFOX and pembrolizumab as peri-operative (pre- and post-operative) therapy in patients with locally advanced adenocarcinoma of distal esophagus, GEJ and stomach is safe and preliminary benefit data are very encouraging with ypRR of 92% and ypCR of 19% and supporting the combination of chemotherapy and Immune checkpoint inhibitor at perioperative setting. Clinical trial information: NCT03488667.