Moonlight: New Data Points for FOLFOX, Nivo/Ipi, FLOT in EGA

The Moonlight trial has found that for metastatic esophagogastric adenocarcinoma (EGA), (1) chemotherapy plus a dual checkpoint inhibitor parallelly administered is associated with an increase in toxicity but not disease activity; (2) the use of sequential chemotherapy followed by immune-oncology monotherapy is insufficient; and (3) FLOT and nivolumab seem to be associated with improved efficacy.

Dr. Sylvie Lorenzen and colleagues aimed to generate signals about whether dual checkpoint inhibition or triplet chemotherapy is more beneficial in the context of nivolumab therapy for esophagogastric adenocarcinoma. Results were presented at the European Society for Medical Oncology Congress 2024.

This multi-cohort treatment optimization trial evaluated FOLFOX plus nivolumab and ipilimumab administered parallelly or sequentially (arm A/A1) compared to FOLFOX alone (arm B) or FLOT plus nivolumab (arm C) for first-line treatment of metastatic or advanced inoperable HER2-negative EGA.

The primary endpoint was progression-free survival (PFS) based on the intent-to-treat population for arm A versus arm B and PFS rate at six months (PFS@6) for arms A2 and C. The main secondary endpoints included PFS, overall survival (OS), and overall response rate (ORR). Disease control rate (DCR) was also measured.

Two-hundred-and-sixty-two patients were randomly assigned 1:1 to:

• Arm A (n=60): modified (m) FOLFOX once every two weeks plus nivolumab 240 mg once every two weeks and ipilimumab 1 mg/kg every six weeks in parallel
• Arm B (n=60): mFOLFOX alone

Patients were subsequently randomly assigned 1:2 to:

• Arm A1 (n=30): Identical to arm A
• Arm A2 (60): Three cycles of mFOLFOX followed by nivolumab once every two weeks and ipilimumab once every six weeks with optimal repetition

Finally, patients were allocated to single arm C (n=52): FLOT once every two weeks plus nivolumab once every two weeks).

IKF-AIO-Moonlight Trial Results

Baseline characteristics were comparable in all arms, and toxicity was manageable in all treatment arms but was increased with dual checkpoint inhibition (details to be presented).