Phase I/II study of nab-paclitaxel combined with S-1 as adjuvant chemotherapy in diffuse type of stage III gastric or gastroesophageal junction adenocarcinoma

e16064 Background: Diffuse type (Lauren's classification) of gastric adenocarcinoma (GAC) or gastroesophageal junction adenocarcinoma (GEJ) has a poorer prognosis than intestinal type of GAC or GEJ. Studies have shown that nab-paclitaxel combined with S-1 has a synergistic anti-tumor effect on advanced gastric cancer. We designed this trial to evaluate the efficacy and safety of nab-paclitaxel plus S-1 as adjuvant chemotherapy in diffuse type of stage III GAC or GEJ. Methods: This study was a multi-center, open-label, phase I/II study. The results of the phase I dose escalation study have already been reported, and the recommended phase II dose (RP2D) of nab-paclitaxel is 260mg/m 2 . Patients with stage III diffuse type GAC or GEJ after D2 dissection and achieved R0 resection were included in this study. S-1 monotherapy was used as adjuvant therapy in the first cycle. If absence of grade3/4 treatment-related adverse events (AEs) of S-1 monotherapy, nab-paclitaxel (260mg/m 2 , d1, q3w) and S-1 [body surface area (BSA) <1.25 m 2 , 80mg/d; BSA 1.25–1.5 m 2 , 100mg/d; BSA >1.5 m 2 , 120mg/d; d1-14, q3w] were administered for 6 cycles. Then patients still received S-1 monotherapy for 8 cycles. In phase II study, the primary endpoint was 1-year disease free survival (DFS) rate, and the secondary endpoints were 3-year DFS rate and safety. Results: From January 2021 to February 2023, a total of 42 patients were enrolled in this analysis (3 patients in nab-paclitaxel 260mg/m 2 dose group in phase I and 39 patients in phase II). The median age (range) was 53 (29~69) years, 18 patients (42.86%) were stage IIIA, 10 patients (23.81%) were stage IIIB and 14 patients (33.33%) were stage IIIC. The median follow-up time was 13.26 months. As of January 2023, 12 patients experienced recurrence. The 1-year-DFS rate was 74.07%, median DFS and 3-year-DFS rate were not reached. The incidence of adverse effects (AEs) was 78.57% (33/42), and the rate of grade 3-4 AEs was 42.86% (18/42). The most common AEs were neutropenia and leukopenia. In addition, we performed next generation sequencing (NGS) for 5 relapsed patients, and 5 non-relapsed patients who were matched to the relapsed patients. The results showed that the mutant rates of tumor supressor gene CDH1, ARID1A, KMT2D, and TP53 in non-relapsed patients were higher than that in relapsed patients. The positive rate of ctDNA were 60% in relapsed patients, but no ctDNA was detected in non-relapsed patients. Conclusions: Adjuvant chemotherapy with nab-paclitaxel and S-1 followed by S-1 monotherapy exhibited promising clinical efficacy, with acceptable tolerability. This study deserves further investigation and follow up for diffuse type of GAC or GEJ. Clinical trial information: NCT03977220 .