1203O - FOLFOX plus nivolumab and ipilimumab versus FOLFOX induction followed by nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: Results from the randomized phase II Moonlight trial of the AIO

Background

FOLFOX plus nivolumab (nivo) has become standard of care for first-line therapy of patients (pts) with esophagogastric adenocarcinomas. To reduce toxicity, there is a need to evaluate if short-term induction chemotherapy followed by immunotherapy as an alternating treatment is as effective, while more tolerable. The aim of this second part of the Moonlight trial was to evaluate if mFOLFOX induction therapy followed by nivo plus ipilimumab (ipi) is less toxic but equally effective compared to both regimens combined together. Results of the other study parts will be presented elsewhere.

Methods

The AIO-STO-0417 trial (Moonlight) is a four-arm investigator-initiated trial, whereof two arms (A1/A2) are presented here. Pts were randomized 1:2 to FOLFOX plus nivo 240 mg; q2w and ipi 1 mg/kg; q6w administered in parallel (arm A1; parallel treatment) or three cycles of mFOLFOX induction treatment followed by nivo and ipi (arm A2; sequential treatment). PD-L1 expression was centrally assessed. Primary endpoint was progression-free survival at 6 months (PFS@6), main secondary endpoints were OS, PFS, objective response rate (ORR) and safety.

Results

Ninety patients were randomized (30 pts to arm A1 and 60 pts to A2). Baseline characteristics were: median age 62y, GEJ, 51%, intestinal type, 33%. Forty-one percent had PD-L1 CPS≥1 (available in 74% of pts). Pts received a median of 11 cycles in A1 vs 7 cycles in A2. Adverse events of grade ≥3 were seen in 93% of the pts for arm A1 and 73% for arm A2, serious adverse events (SAE) in 70% in arm A1 and 62% in A2. Median follow-up was 7.3 mo. PFS@6 was 57% in arm A1 vs 28% in A2 (p=.012) with median PFS 8.4 vs 4.0 mo, respectively (p=.006). Median OS was not yet reached in A1 vs 9.1 mo in A2, ORR was 47% vs 30%, respectively. The results were similar in the PD-L1+ group.

Conclusions

FOLFOX chemotherapy plus nivolumab and ipilimumab administered in parallel was clearly more effective than FOLFOX induction followed by nivo and ipi. Although associated with lower toxicity, our study doesn’t support the use of sequential treatment in the first-line setting.

Clinical trial identification

EudraCT-No. 2017-002080-18 NCT03647969.

Editorial acknowledgement

Legal entity responsible for the study

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest.

Funding

Bristol-Myers Squibb.

Disclosure

P.C. Thuss-Patience: Financial Interests, Personal, Advisory Board: Novartis, MSD, Bristol-Myers Squibb, Merck Serono, Roche, Astellas Pharma, Servier, Daiichi Sankyo, Pfizer, Lilly; Financial Interests, Institutional, Research Grant: Novartis, Merck Serono. G. Folprecht: Financial Interests, Personal, Advisory Board: Bayer, BMS, Exact Sciences, Merck, MSD, Pierre Fabre, Roche / Genentech, Sanofi-Aventis, Servier; Financial Interests, Personal, Invited Speaker: Falk Foundation, Lilly, Roche / Genentech. E. Goekkurt: Financial Interests, Personal, Advisory Board: MSD, Bristol-Myers Squibb, Roche, Sanofi . T.J. Ettrich: Financial Interests, Personal, Advisory Board: Eisai, MSD, Bayer, Roche, Sanofi, Bristol-Myers Squibb, Celgene, Incyte, AstraZeneca, Merck Serono, Pierre Fabre, Servier, Lilly, Ipsen; Financial Interests, Personal, Other: Ipsen; Financial Interests, Personal, Research Grant: Baxalta/Shire . D. Pink: Financial Interests, Institutional, Invited Speaker: Blueprint, PharmaMar; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim, PharmaMar, Roche; Financial Interests, Institutional, Principal Investigator: BMS, EUSA-Pharma, Lilly, PharmaMar, Roche; Financial Interests, Institutional, Project Lead: Novartis; Non-Financial Interests, Personal, Member: ASCO, Connective Tissue Oncology Society (CTOS), Deutsche Krebsgesellschaft - German Cancer Society (DKG), Deutsche Sarkomstiftung (DSS). T.O. Götze: 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; Financial Interests, Personal, Research Grant: Deutsche Forschungsgemeinschaft, Gemeinsamer Bundesausschuss, Deutsche Krebshilfe, Lilly, AstraZeneca, Incyte. S. Al-Batran: Financial Interests, Personal, Advisory Board: Lilly, Bristol-Myers Squibb, Merck Sharp & Dohme, MacroGenics; Financial Interests, Personal, Advisory Role: Astra/Daichii ; Financial Interests, Personal, Speaker’s Bureau: Lilly, AIO gGmbH, Bristol-Myers Squibb, MCI Group ; Financial Interests, Personal, Ownership Interest: Institut für Klinische Krebsforschung GmbH ; Financial Interests, Personal, Research Grant: Celgene, Lilly, Medac, Hospira, Sanofi, German Cancer Aid, German Research Foundation, Federal Ministry of Education and Research, Roche, Vifor Pharma, Eurozyto, Immutep, Ipsen, Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca. All other authors have declared no conflicts of interest.