Modified FOLFOX plus/minus nivolumab and ipilimumab vs FLOT plus nivolumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: The randomized phase 2 IKF-S628 Moonlight trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

person Sylvie Lorenzen Klinikum rechts der Isar, Technische Universität München, Klinik für Innere Medizin III, München, Germany info_outline Sylvie Lorenzen, Thorsten Oliver Goetze, Peter C. Thuss-Patience, Jorge Riera-Knorrenschild, Eray Goekkurt, Tobias Nicolaas Dechow, Thomas Jens Ettrich, Ralf Dieter Hofheinz, Kim Barbara Luley, Daniel Pink, Udo Lindig, Gunnar Folprecht, Gunter Schuch, Michael Bitzer, Volker Heinemann, Stefan Angermeier, Claus Bolling, Sabine Junge, Claudia Pauligk, Salah-Eddin Al-Batran

Authors person Sylvie Lorenzen Klinikum rechts der Isar, Technische Universität München, Klinik für Innere Medizin III, München, Germany info_outline Sylvie Lorenzen, Thorsten Oliver Goetze, Peter C. Thuss-Patience, Jorge Riera-Knorrenschild, Eray Goekkurt, Tobias Nicolaas Dechow, Thomas Jens Ettrich, Ralf Dieter Hofheinz, Kim Barbara Luley, Daniel Pink, Udo Lindig, Gunnar Folprecht, Gunter Schuch, Michael Bitzer, Volker Heinemann, Stefan Angermeier, Claus Bolling, Sabine Junge, Claudia Pauligk, Salah-Eddin Al-Batran Organizations Klinikum rechts der Isar, Technische Universität München, Klinik für Innere Medizin III, München, Germany, Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, and Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt, Germany, Charité–Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany, Universitätsklinikum Marburg, Klinik für Innere Medizin, Marburg, Germany, Hämatologisch-Onkologische Praxis Eppendorf (HOPE) and Universitäres Cancer Center Hamburg (UCCH), Hamburg, Germany, Onkologie Ravensburg, Ravensburg, Germany, Ulm University Hospital, Department of Internal Medicine I, Ulm, Germany, Universitätsmedizin Mannheim, Tagestherapiezentrum am ITM, Mannheim, Germany, University Hospital Schleswig-Holstein, Campus Luebeck, Lübeck, Germany, Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie, Transplantationszentrum, Palliativmedizin, Universität Greifswald and Klinik für Hämatologie, Onkologie und Palliativmedizin-Sarkomzentrum, HELIOS Klinikum Bad Saarow, Bad Saarow, Germany, Universitätsklinikum Jena, Klinik für Innere Medizin II, Jena, Germany, Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Dresden, Germany, Hämatologisch-Onkologische Praxis Altona (HOPA), Hamburg, Germany, Universitätsklinikum Tübingen, Medizinische Klinik I, Tuebingen, Germany, Klinikum der Universität München-Großhadern, Medizinische Klinik III, München, Germany, Klinikum Ludwigsburg, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Pneumologie, Diabetologie und Infektiologie, Ludwigsburg, Germany, Agaplesion Markus Krankenhaus, Hämatologie/Onkologie, Frankfurt, Germany, Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, Frankfurt, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Bristol-Myers Squibb Background: FOLFOX plus nivolumab has become standard of care for first-line therapy of patients (pts) with esophagogastric adenocarcinomas (EGA). The AIO-STO-0417 trial (Moonlight) is a multi-cohort treatment optimization trial that evaluates the combination of FOLFOX alone (Arm B) vs FOLFOX plus nivolumab (nivo) and ipilimumab (ipi) administered in parallel (Arm A/A1) or sequentially (Arm A2) and FLOT plus nivolumab administered in parallel (Arm C) for 1L-treatment of metastatic or advanced inoperable Her-2 negative EGA. The aim is to generate signals whether a. dual checkpoint inhibition or b. a triplet chemotherapy is beneficial in the context of nivolumab therapy for this disease. Methods: Pts were randomized 1:1 to Arm A (mFOLFOX q2w plus nivo 240 mg q2w + ipi 1 mg/kg q6w administered in parallel) or B (mFOLFOX alone). In a subsequent phase pts were randomized 1:2 to Arm A1 (identical to Arm A) or A2 (three cycles of mFOLFOX followed by nivo q2w + ipi q6w, with optional repetition). In a final phase, all pts were allocated to single Arm C (FLOT q2w + nivo q2w). The primary endpoint was progression-free survival (PFS) based on the ITT population for Arm A vs Arm B and PFS rate at 6 months (PFS@6) for Arms A2 and C. Main secondary endpoints were PFS and ORR. Here, we present results for Arms A/A1, A2 and B. Results: A total of 262 pts were enrolled, Arm A (n=60), Arm B (n=60), Arm A1 (n=30), Arm A2 (n=60) and Arm C (n=52, results presented elsewhere). Baseline characteristics were comparable in all arms. Overall PD-L1 expression (CPS ≥1) was low with 41% and balanced between Arms A/A1, A2 and B. Analysis of pooled Arms A/A1 (n=90) showed an increase in toxicity (pts with AEs grade ≥3 88% vs 65% in Arm B and 75% in Arm A2, treatment related SAEs grade ≥3 A/A1 41% vs B 18% vs A2 17%) but not in activity. Arm A/A1 compared with Arm A2 was more effective in terms of PFS@6 (48% vs 30%), median PFS 5.8 vs 4.0 months and objective response rate (ORR) 46% vs 30%. Conclusions: Albeit the small number of pts in each cohort we conclude that in the first-line setting of metastatic EGA. a) Chemo plus dual checkpoint inhibition administered in parallel is associated with an increase in toxicity but not activity. b) Although associated with lower toxicity the use of sequential chemo followed by IO monotherapy is insufficient. The relatively low numbers of patients with PD-L1 CPS ≥1 may have impacted these results. Clinical trial information: NCT03647969.

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