PURPOSE: Immune checkpoints inhibitors (ICIs) combined with chemotherapy have provided successful results in patients with gastric and gastroesophageal junction (G/GEJ) cancers in the metastatic setting. Similar strategies have been explored in earlier stages. Here, we present final results of the phase II MONEO trial, which evaluated the addition of avelumab to neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients with untreated, resectable G/GEJ adenocarcinoma received neoadjuvant treatment with four cycles of avelumab plus the FLOT4 regimen, followed by surgery. Upon postoperative recovery, patients underwent four additional adjuvant cycles of the same combination, followed by avelumab monotherapy for up to one year. The primary endpoint was pathological complete response (pCR) rate. Sequential flow cytometry and cytokine determination were performed in peripheral blood, along with multiplex tissue immunofluorescence and RNA sequencing (RNA-seq) in tumor specimens. RESULTS: Forty patients were enrolled, achieving a pCR rate of 21.1% (95% CI: 10.0-37.0). Major pathological response rate was 28.9%, more pronounced in those patients with tumors expressing programmed cell death protein 1 (PD-L1) before treatment as measured by combined positive score (CPS cut-off 10
33.3% vs. 21.1%). Results propose several potential biomarkers considering tumor immune infiltrate, circulating immune cells, and cytokines. Eighty percent of patients experienced treatment-related grade ≥3 adverse events. CONCLUSIONS: The combination of avelumab plus the FLOT4 regimen showed relatively modest efficacy in resectable G/GEJ adenocarcinoma. Better results were observed in PD-L1 CPS ≥10% tumors. Exploratory biomarker analyses provide insights that may help to identify candidates most likely to benefit from chemoimmunotherapy as a neoadjuvant treatment.