Neoadjuvant toripalimab plus CapeOX in patients with locally advanced EBV-positive gastric or esophagogastric junction adenocarcinoma (GC/EGJC): Results from the phase II NICE trial.

4069 Background: Surgery remains the cornerstone of curative therapy for locally advanced GC/EGJC. EBV-positive tumor is a distinct molecular subtype that would be potentially sensitive to immunotherapy, but no consistent reports. Given that chemotherapy may enhance antitumor immunity, perioperative immunochemotherapy may be a promising modality for EBV-positive patients. Methods: The NICE trial is a multicenter, multi-cohort phase II study (NCT04744649) evaluating the safety and efficacy of toripalimab plus CapeOX as perioperative treatment in patients with locally advanced GC/EGJC. The Cohort B was first of its kind to assess the efficacy of the immunochemotherapy on the EBV-positive GC/EGJC , in which patients received toripalimab (240 mg) combined with standard-dose CapeOX every 3 weeks for 4 cycles preoperatively and 4 cycles postoperatively. Eligibility criteria included clinical tumor stages of cT3-4aNxM0 or cT2N+M0 disease as determined by both imaging scan and staging laparoscopy with negative peritoneal cytology. The primary endpoint was major pathologic response (MPR, defined as < 10% viable tumor cells). The tumor immune microenvironment (TIME) of tissue samples obtained before and after treatment was analyzed using multiple immunofluorescence assays to assess changes in immune cell infiltration and other biomarkers related to treatment response. Results: From May 2021 to September 2023, 17 patients with EBV-positive GC/EGJC (GC, n = 15; EGJC, n = 2) were enrolled, with cT2N0 (n = 1), cT3N1-3 (n = 5), and cT4aN1-3 (n = 11). All patients completed 4 preoperative cycles of treatment, and none experienced progression before surgery. Only one patient withdrew the inform content after preoperative therapy, the 16 patients underwent radical resection, achieving a 100% R0 resection rate (16/16). The MPR rate was 37.5% (6/16), and pathological complete response rate (pCR) was 25.0% (4/16). Of the 16 participants, 15 received postoperative adjuvant therapy, while 1 declined further treatment. The TIME analysis results showed that tumor-infiltrating CD8+ T cells in post-treatment tumor tissues significantly clonally expanded compared with pre-treatment paired tissues. Treatment-related grade 3/4 adverse events were observed in 6 patients (35.3%, 6/17). Until Dec 31 2024, none of the patients experienced disease recurrence. Conclusions: Neoadjuvant toripalimab combined with CapeOX is a safe and effective treatment option for patients with EBV-positive, locally advanced GC/EGJC, with moderate MPR and pCR, indicating further investigating for this distinct type of cancer. Clinical trial information: NCT04744649 .