Efficacy and safety of anti-PD-1 combined with thymosin and SOX in neoadjuvant treatment of cStage III gastric or esophagogastric junctional adenocarcinoma (NAPTSOX24): A prospective, open-label, single-arm, phase II clinical study.

Abstract

e16032 Background: Neoadjuvant immunochemotherapy shows increasing potential in improving resectability and outcomes in gastric cancer, however the clinical benefits may depend on PD-L1 expression. This prospective, single-arm, phase II trial aims to evaluate efficacy and safety of combining the PD-1 inhibitor serplulimab, thymosin α1, and SOX regimens in HER2-negative cStage III gastric or esophagogastric junctional (G/EGJ) adenocarcinoma. Methods: From June to December 2024, all 30 cases were enrolled. Participants are designed to receive 3 cycles of serplulimab (300 mg, Q3W), thymosin α1 (4.8 mg, BIW) and SOX regimen. Radical gastrectomy plus D2 lymphadenectomy will be performed 2–6 weeks post-treatment. Key outcomes include pathological responses (pCR/MPR) and treatment-related adverse events (TRAEs). Results: Median age of all the 30 cases was 66 years (37–75), 90% (27/30) were male, and 46.7% (14/30) had EGJ tumors. Median PD-L1 CPS was 3 (0–30), and 93.3% (28/30) were pMMR/MSS. As of the cutoff date, TRAEs were reported in 66.7% (20/30) cases, with diarrhea (46.7%, 14/30) being the most frequent, followed by decreased appetite (23.3%, 7/30) and neutropenia (20.0%, 6/30). No grade 5 TRAEs occurred. Immune-related adverse events were only reported in 10% (3/30) cases. Till now, 53.3% (16/30) patients have undergone curative gastrectomy, with 25.0% (4/16) achieving pCR and 37.5% (6/16) demonstrating MPR. Patients with intestinal Lauren type exhibited a significantly better drug response (P = 0.007, Table 1). The variation in CD3+ T cell count was significantly higher in patients with pCR/MPR (P = 0.036), suggesting a better predictive value for pathological responses than PD-L1 expression and microsatellite instability status. Conclusions: Combination of anti-PD-1, thymosin α1, and SOX regimen promising efficacy with manageable toxicity in the neoadjuvant setting of locally advanced G/EGJ cancer, independent of PD-L1 expression. Ongoing follow-up will further assess its clinical benefits and safety. (ClinicalTrials.gov identifier: NCT06461910). Clinical trial information: NCT06461910 . Baseline characteristics and pathological response outcomes. Variables Total (n=16) pCR (n=4) MPR (n=6) Others (n=6) P value Age (median/range) 63.5 (37-75) 65.5 (61-71) 66.0 (37-75) 59.0 (47-74) 0.761 Sex (Female/male) 1/15 0/4 0/6 1/5 0.411 H.P infection (No/Yes) 5/11 1/3 2/4 2/4 0.953 Borrmann (I/II/III) 2/8/6 0/3/1 2/3/1 0/2/4 0.172 Lauren (Diffuse/Intestinal/Mixed) 3/8/5 0/2/2 0/6/0 3/0/3 0.007* Pretreated cStage (IIIa/IIIb) 9/7 1/3 3/3 5/1 0.176 MMR (MSI/MSS) 1/15 0/4 0/6 1/5 0.411 PD-L1 CPS (0/1~5/>5) 5/5/6 2/1/1 1/4/1 2/0/4 0.115