Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK

TPS4142 Background: Perioperative FLOT chemotherapy has become a standard of care for locally advanced, resectable gastric cancer and adenocarcinoma of the GEJ. However, patient outcomes are still unsatisfactory and 5-year survival in T3-4 or nodal positive disease is still around 50%. Targeting the PD-1/PD-L1 pathway has proven active in different cancers, including esophagogastric cancer, and was associated with response rates in the 10-15% range in unselected, heavily pre-treated gastric cancer patients. Atezolizumab is a PD-L1 inhibitor with established efficacy and tolerability profiles. This study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with FLOT. Methods: This is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Eligibility status is centrally evaluated. Patients are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m²) followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS) as assessed by the Kaplan-Meier-Method. The statistical design is based on a target HR of 0.68, a power of 0.8, and a significance level of p< 0.05 (1-sided log rank test). A total of 295 patients will be randomized. Main secondary endpoints are rates of centrally assessed pathological regression (rates of complete and nearly complete pathological regression), overall survival, R0 resection, and safety. Recruitment started in Sept 2018; by February 2019, a total of 27 patients have been randomized. Clinical trial information: NCT03421288.