Toripalimab plus docetaxel, oxaliplatin, and capecitabine for untreated metastatic gastric and esophagogastric junction adenocarcinoma: A TORNADO study.

Abstract

e16004 Background: Chemotherapy and PD-1 inhibitor have shown significant clinical benefits in first-line treatment of metastatic gastric and esophagogastric junction adenocarcinoma. The prospective, open-lable, single-arm, single-center clinical trial was designed to assess efficacy and safety of Toripalimab plus docetaxel, oxaliplatin and capecitabine. Methods: Eligible criteria were treatment histopathologically confirmed stage IV(AJCC8) and ECOG 0-2, HER2 negative, regardless of CPS expression of untreated metastatic gastric and esophagogastric junction adenocarcinoma. Patients were given with Docetaxel (75mg/m2, iv,d1), Oxaliplatin(130mg/m2, iv,d1), Capecitabine (750mg/m2 bid, po,d1-d14) combined with Toripalimab (240mg, iv,d4), every 3 weeks. Dexamethasone 4.5mg, q12h, po. started at the night before docetaxel administrated for 3 days. Tumor response was assessed every 2/4 cycles by radiologic imaging. After 4 cycles, MDT was employed to determine subsequent treatment plan. Primary endpoints were ORR (investigator-assessed RECIST 1.1) and safety. The secondary endpoints were progression-free survival and overall survival. Results: 30 patients were enrolled up to 6/1/2025. The median follow-up was 11.7month (range 1.1-61.4). The median age was 57 years (range 32-78), male was 53.3%.The proportion of ECOG 1 patients accounted for 60%, ECOG 2 for 23.3%. A total of 22 patients completed 4 cycles treatment, and 26 patients were eligible for efficacy assessment. Confirmed ORRs were 73.1% (95% CI: 53.9,86.3) and DCR were 96.2% (95%CI: 81.1, 99.3). 57.7% of patients had a disease response depth greater than 50%. Median PFS was 8.5 month (95% CI: 6.76-10.19), the 6-month and 12-month PFS rate was 72.4% and 29.0%, respectively. Median OS was 11.03 month (95% CI: 9.45,12.63) , the 6-month and 12-month OS rate was 80.0% and 43.3%, respectively. The OS of patients completed 4 cycles could reach 18 monthsThe overall incidence of adverse events is 86.7%, Gr ≥3 AEs were seen in 46.7% of patients, Gr 5 AEs were not observed. The most common treated-related AEs were Diarrhea (26.7%) and Platelet count decreased (26.7%). The most common immune-related AEs were Rash (10%). Conclusions: These results showed favorable tumor response, higher ORR, DCR, tumor response depth. The possible reasons were the use of immunotherapy on the 4 th day and the combination with docetaxel. Compared to other GC immunotherapy-related studies, there was no advantage in OS for all patients, while PFS and completed 4 cycles patients' OS were superior to others. The safety of Toripalimab plus docetaxel, oxaliplatin and capecitabine was consistent with each agents known safety profile; no new safety signals were identified. Clinical trial information: ChiCTR2000030877 .