Preliminary results from phase 2 study of prolonged neoadjuvant immunotherapy plus chemotherapy in Borrmann type 4 and large type 3 gastric cancer (Neo-ICEBOAT Study).

e16108 Background: Treatment options for Borrmann Type 4 gastric cancer (Linitis Plastica) have long been a topic of debate. This patient group is characterized by diffuse cancer infiltration throughout the stomach, early metastasis, and a poor prognosis. In this study, we aim to evaluate the efficacy and safety of combining immunotherapy with chemotherapy for patients with Borrmann Type 4 (B-IV) or large Type 3 (B-III) gastric cancer. Methods: Patients (pts) diagnosed with gastric adenocarcinoma (B-IV or B-III) without distant metastasis were eligible for the study. Participants received a prolonged neoadjuvant treatment regimen consisting of the anti-PD-1 inhibitor (ICI) Tislelizumab and platinum-based chemotherapy (oxaliplatin combined with either capecitabine or S-1) administered in 3-week cycles. After completing six cycles, patients underwent radical surgery. The primary endpoint was the pathological response rate, assessed using the tumor regression grade (TRG) system. Results: As of January 2025, 42 pts were enrolled in this trial (intention-to-treat group), of whom 27 completed the neoadjuvant treatment and underwent radical gastrectomy. Among the 27 pts, 17 completed all the 6 cycles of neoadjuvant treatment, while 5 pts completed either 3-4 cycles or 5 cycles. All 42 pts were included in the safety and demographics analysis, while 27 were included in the efficacy analysis. The median age was 59 (range: 31–73), with 57% male. All pts had an ECOG performance status of 0 or 1, and 79% (33 pts) were B-IV. Lauren’s histological classification included intestinal (12 pts), diffuse (18 pts), and mixed (9 pts) types. 38 pts showed proficient mismatch repair proteins(pMMR, the other 4 not evaluated). Following surgery, all 27 pts had R0 resection. 11 of 27 pts (41%) demonstrated a pathological response of TRG 0/1 (95% CI: 24%–59%), exceeding the prespecified endpoint. Pts with a PD-L1 CPS score ≥5 or < 5 showed a comparable percentage of those with TRG 0/1. Notably, 7 pts (26%) achieved ypTNM stage 0 (pCR), and 18 pts (67%) were ypN0. A significantly higher pathological response rate (TRG 0/1) was observed in pts with Lauren’s intestinal or mixed types (9/16, 59%; 95% CI: 36%–78%) compared to those with diffuse type (2/11, 18%; 95% CI: 3%–48%; p < 0.05). Treatment-related adverse events were reported in 35 of 42 pts (83%), with common events including thrombocytopenia, nausea, and liver injury. 7 pts (17%) experienced grade 3/4 adverse events. 5 pts (18%) underwent surgical morbidity including bleeding, anastomotic leak and infection. Conclusions: Prolonged neoadjuvant treatment with ICI Tislelizumab combined with platinum-based chemotherapy demonstrated promising clinical efficacy and a manageable safety profile in pts with B-IV or large B-III gastric cancer. The study is ongoing and up to 53 pts will be enrolled into this cohort. Clinical trial information: NCT06451211 .