Updated results of perioperative PD-1 antibody toripalimab plus FLOT chemotherapy for locally advanced resectable gastric or gastro-esophageal junction adenocarcinoma: A one-arm open-table phase II trial.

e16128 Background: Perioperative chemotherapy is the standard treatment for resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. Immune checkpoint inhibitors have activity in advanced gastric/GEJ cancer. This trial to assess the efficacy of the addition of toripalimab to FLOT for resectable patients and explore the immune microenvironment prospectively related to treatment response of neoadjuvant immunotherapy by multiplex immunohistochemistry. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥ cT2 or cN+) were enrolled to receive 4 pre- and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m 2 ; oxaliplatin 85 mg/m 2 ; leucovorin 200 mg/m 2 ; 5-Fu 2600 mg/m 2 , q2w). The primary endpoint were 3-year disease-free survival rate, overall survival and pathological complete response rate (pCR). Planned sample size of 36 operated patients. if the pCR rate is greater than 16% (n = 6), an additional 20 cases will be added. Multiplex immunohistochemistry is used to quantify in situ biomarker at subcellular resolution. Results: Study accrual completed at August 2022, 55 patients were enrolled, 40M/15F, age 57 (28-76), ECOG 0 (39) and 1 (16). 4 patients had not received surgery were excluded from efficacy analysis (Three patients withdrew consent after two treatment cycles and one refused surgery after 4 cycles pre-operative treatment). Fifty-one had completely neoadjuvant treatment and received surgery. Pathological response was TRG 0/ 1/ 2/ 3 in 10/ 6/ 21/ 14 patients with pCR seen in 10 (19.6%). Major pathologic response (TRG 0 and 1) was seen in 16 (31.4%) patients. At 36.6 (17.6-57.8) months follow up, the median disease-free survival (DFS) and overall survival (OS) were not reached for all patients. DFS rate at 1, 2, and 3 year is 78.4%, 56.9%, and 54.3%. OS rate at 1, 2, and 3 year is 94.1%, 69.5%, and 65.2%. Compared with TRG 2 or 3, patients with MPR showed significant longer survival (p = 0.01). Twenty-four patients underwent immune microenvironment analysis on their pre-treatment specimens by multiplex immunohistochemisty. Compared with TRG 2 or 3 (n = 11), NK cells with positive CD56 expression in tumor parenchyma microenvironment in patients with MPR (n = 13) were significant decreased (p = 0.024). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate in patients with resectable gastric/GEJ adenocarcinoma. MPR rate and NK cells in tumor microenvironment have a predictive on therapeutic efficacy, with deserves further study. Clinical trial information: NCT04354662 .