LBA59 - 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: Final results of the IKF-AIO-Moonlight trial

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, evaluating: 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 (Arm C) for 1L-treatment of metastatic or advanced inoperable Her-2 negative EGA. The aim was 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). Subsequently pts were randomized 1:2 to Arm A1 (identical to Arm A) or A2 (3 cycles of mFOLFOX followed by nivo q2w + ipi q6w, with optional repetition). Finally, 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, OS and ORR.

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). Baseline characteristics were comparable in all Arms. Median PFS/OS were: Arm A/A1 5.8/10.1, A2 4.0/7.6, B 6.6/12.5 and C 7.0/14.6 months. ORR/DCR were: A/A1 49%/78%, A2 32%/75%, B 47%/70% and C 56%/87%: Toxicity was manageable in all treatment Arms, but was increased with dual checkpoint-inhibition (details will be presented).

Conclusions

Albeit the small number of pts in each cohort we conclude: a) Chemo plus dual checkpoint inhibition administered in parallel is associated with an increase in toxicity but not activity. b) The use of sequential chemo followed by IO monotherapy is insufficient. c) FLOT and nivolumab is feasible and seems to be associated with improved efficacy.

Clinical trial identification

Trial Protocol No: AIO-STO-0417/IKF628; NCT03647969.

Editorial acknowledgement

Legal entity responsible for the study

Frankfurter Institut für Klinische Krebsforschung IKF GmbH.

Funding

Bristol Myers Squibb.

Disclosure

S. Lorenzen: Financial Interests, Personal, Invited Speaker: Servier, Lilly, MSD, BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: Astellas. T.O. Goetze: Financial Interests, Personal, Advisory Board: Lilly, MSD Oncology, Bayer, Servier, Roche, Novartis, Incyte, Foundation Medicine, Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Lilly, MSD Oncology; Financial Interests, Personal, Research Grant: Deutsche Forschungsgemeinschaft, Gemeinsamer Bundesausschuss, Deutsche Krebshilfe, Lilly, AstraZeneca, Incyte. E. Goekkurt: Financial Interests, Institutional, Advisory Board: MSD, BMS, Daiichi, Servier, Amgen, Novartis; Financial Interests, Institutional, Local PI: msd, Daiichi, AstraZeneca, BMS, Novartis. T.J. Ettrich: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Bayer, Amgen, MSD, Merck, Ipsen, Sanofi Aventis, Pierre-Fabre Pharma, Incyte, Lilly, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD, Ipsen, Eisai; Financial Interests, Institutional, Research Grant: Servier. R.D. Hofheinz: Financial Interests, Personal, Advisory Board: Amgen, BMS, MSD, Sanofi, Roche, AstraZeneca, Lilly, Roche, merck, Daichi, Nordic Pharma, AbbVie, BeiGene. D. Pink: Financial Interests, Institutional, Invited Speaker: Blueprint, PharmaMar, Boehringer Ingelheim, Deciphera; Financial Interests, Institutional, Advisory Board: Roche, PharmaMar, Boehringer Ingelheim; Financial Interests, Institutional, Coordinating PI: BMS, Recordati, PharmaMar, Lilly, Roche, Boehringer Ingelheim; Financial Interests, Institutional, Other, scientific lead of a trial with funding from Novartis: Novartis; Non-Financial Interests, Project Lead: Institut für Klinische Forschung Frankfurt; Non-Financial Interests, Member: ASCO, Deutsche Krebsgesellschaft - German Cancer Society (DKG), Connective Tissue Oncology Society (CTOS), Deutsche Sarkomstiftung (DSS). S. Al-Batran: Financial Interests, Personal, Advisory Board: Lilly, Bristol Myers Squibb, MSD Sharp & Dohme; Financial Interests, Personal, Invited Speaker: MCI Deutschland GmbH; Financial Interests, Personal, Ownership Interest, CEO: Institut für Klinische Krebsforschung IKF GmbH; Financial Interests, Institutional, Research Grant: Sanofi, Roche, Celgene, Lilly, Eurozyto, Immutep, Ipsen, Bristol Myers Squibb, MSD Sharp & Dohme, AstraZeneca, German Cancer Aid (Krebshilfe), German Research Foundation, Federal Ministry of Education and Research. All other authors have declared no conflicts of interest.