Neoadjuvant PD-1 inhibitor tislelizumab combined with s-1 plus oxaliplatin in patients with local advanced gastric cancer or gastroesophageal junction adenocarcinoma: Interim results of a single-arm, phase II trial.

300 Background: D2 radical surgery and adjuvant chemotherapy is mainly treatment scheme of Gastric/gastroesophageal junction (G/GEJ) cancer. Nevertheless, the prognosis of patients with G/GEJ cancer still remain variation after normative therapy. Further, neoadjuvant therapy showed highlighted application value and Immuno-oncology therapy is newly prominent in improving prognosis of patients with G/GEJ cancer recently. Methods: We conduct a prospective, single-arm, open-label, non-randomized phase II trials of PD-1 inhibitor Tislelizumab combined with S-1 plus Oxaliplatin (SOX) in Patients with Local Advanced G/GEJ cancer (NCT04890392). Treatment is performed for 3 cycles (21 days/1 cycle) and all patients are evaluated tumor pathology regression after D2 radical surgery performed, and are followed up. The primary endpoints were tumor major pathology response (MPR) and other events of tumor response assessed by tumor regression grade (TRG). We also recode the variation of immunological indicators during treatment and develop a predictive nomogram to predict the probability of patients reached MPR. Results: 13 of 21 patients (61.9%) reached MPR after treatment and 5 of 21 patients had a complete tumor response (23.8%). While 2 of 21 patients were assessed as disease progression (9.5%). there was no significant difference in MPR (TRG = 0&1) between gastric cancer and gastroesophageal junction cancer (6/11 vs. 7/10. P = 0.525). Adverse events occurred in 11 of 21 patients (52.4%) in the cohort. Grade III-IV adverse event occurred in only 1 of 21 patients (4.8%). the variation of CD3+ and CD4+ immune cell counts and TNFα of patients reached MPR was significantly higher than patients not reached MPR during treatment (CD3+, P = 0.044; CD4+, P = 0.042; TNFα, P = 0.048). Further, we developed the predictive nomogram of MPR consisted of age, Hb and TNFα and the AUC of nomogram was 0.890; the C-index was 0.885. Conclusions: Neoadjuvant PD-1 Inhibitor Tislelizumab combined with SOX shows greatly potential of therapeutic application in patients with G/GEJ cancer with no-increasing treatment-related adverse events. While this predictive nomogram may help therapists more accurately apply this scheme and explore improvement. Clinical trial information: NCT04890392.