A randomized, open-label phase II/III efficacy and safety study of atezolizumab in combination with FLOT versus FLOT alone in patients with gastric cancer and adenocarcinoma of the oesophagogastric junction and high immune responsiveness: The IKF633/DANTE trial, a trial of AIO in collaboration with SAKK.

person Salah-Eddin Al-Batran Frankfurt Institute of Clinical Cancer Research, Krankenhaus Nordwest, University Cancer Center Germany, Frankfurt, Germany info_outline Salah-Eddin Al-Batran, Sylvie Lorenzen, Vera Heuer, Stefan Angermeier, Thomas Jens Ettrich, Nils Homann, Georg Martin Haag, Annika Kurreck, Alexander Stein, Volker Heinemann, Ulrich Ronellenfitsch, Thomas Zander, Stefan Kubicka, Alexander Rheinhard Siebenhuener, Christina Kopp, Claudia Pauligk, Thorsten Goetze

Authors person Salah-Eddin Al-Batran Frankfurt Institute of Clinical Cancer Research, Krankenhaus Nordwest, University Cancer Center Germany, Frankfurt, Germany info_outline Salah-Eddin Al-Batran, Sylvie Lorenzen, Vera Heuer, Stefan Angermeier, Thomas Jens Ettrich, Nils Homann, Georg Martin Haag, Annika Kurreck, Alexander Stein, Volker Heinemann, Ulrich Ronellenfitsch, Thomas Zander, Stefan Kubicka, Alexander Rheinhard Siebenhuener, Christina Kopp, Claudia Pauligk, Thorsten Goetze Organizations Frankfurt Institute of Clinical Cancer Research, Krankenhaus Nordwest, University Cancer Center Germany, Frankfurt, Germany, Technical University of Munich, School of Medicine, Department of Internal Medicine, Munich, Germany, St. Anna Hospital Herne, Herne, Germany, RKH-Clinics Ludwigsburg, Clinic for Hematology and Oncology, Ludwigsburg, Germany, University Hospital Ulm, Department of Internal Medicine I, Ulm, Germany, Clinical center Wolfsburg, Med. Clinic II, Wolfsburg, Germany, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany, Charité-University madicine Berlin, Department of Hematology, Oncology and Tumorimmunology, Berlin, Germany, Hematology Oncology Practice Eppendorf and University Cancer Center Hamburg (UCCH), Hamburg, Germany, Department of Hematology and Oncology, LMU Klinikum, University of Munich, Comprehensive Cancer Center, Munich, Germany, University Hospital Halle (Saale) and Medical Faculty of the Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany, University Hospital Cologne, Clinic I for Internal Medicine, Cologne, Germany, District Clinic Reutlingen, Medical Clinic I, Reutlingen, Germany, Clinic for Hematology und Onkology, Hirslanden Zürich AG, and Swiss Group for Clinical Cancer Research (SAKK), Zürich, Switzerland, Frankfurt Institute of Clinical Cancer Research IKF at Northwest Hospital, Frankfurt Am Main, Germany, University Cancer Center Frankfurt, and Frankfurt Institute of Clinical Cancer Research IKF at Northwest Hospital, Frankfurt, Germany Abstract Disclosures Research Funding Hector Stiftung F. Hoffmann-La Roche Ltd Background: Despite recent advances, long-term survival of patients with locally advanced, operable esophagogastric adenocarcinoma (EGA) is below 50%. Immune checkpoint inhibitors in the neoadjuvant setting of this tumor type have lately been shown to increase pathological responses in all comers (IKF633/DANTE pII, KEYNOTE-585, Matterhorn), but the effect on survival is still unknown. The IKF633/DANTE pIII trial evaluates the efficacy and clinical activity of atezolizumab (ATZ) with perioperative FLOT in patients (pts) with locally advanced, resectable EGA considered having an immune-responsive profile. Methods: IKF633/DANTE is conducted as a randomized, multinational, multicenter, prospective, investigator-initiated, open label phase II/III trial. For the phase III portion, pts with histologically confirmed EGA of a clinical stage ≥cT2 and/or cN+ without evidence of distant metastases and with at least one immune response criterium (MSI, PD-L1 CPS≥1, TMB ≥10/MB or EBV+) are eligible. Pts are stratified acc. to nodal stage (cN- vs. cN+), tumor site (GEJ type I vs. GEJ type II/III vs. gastric) and PD-L1 expression levels (CPS≥5 vs. CPS<5). Pts are randomized 1:1 to receive 4 pre- and post-operative cycles FLOT/ATZ, followed by 8 cycles ATZ maintenance (Arm A) or 2x4 perioperative cycles FLOT alone (Arm B). In total, 556 pts will be enrolled, thereof 379 pts in phase III. This estimates to a recruitment time of 30 months plus 18 months follow-up for 80% statistical power and a significance level of p<0.05 (two-sided log rank test). The primary endpoint is event-free survival (EFS) with a target hazard ratio of 0.72, reflecting a clinically relevant improvement to 41.65 months in arm A. Main secondary endpoints are pCR, overall survival (OS) also in high immune-responsive subgroups (CPS ≥5/ CPS≥ 10/ MSI), R0 resection rate and safety/tolerability. In addition, a prospective biomarker study with serial circulating tumor DNA (ctDNA) analysis accompanying therapy is performed to explore the prognostic impact of ctDNA on efficacy and survival parameters, as well as on relapse incidence. Recruitment of phase III started in Aug 2023 and is still ongoing. Clinical trial information: NCT03421288.