Feasibility Study of Trifluridine/Tipiracil and Zolbetuximab as Third- or Later-Line Chemotherapy for CLDN18.2-Positive and HER2-Negative Gastric or Gastroesophageal Junction Adenocarcinoma: A Study Protocol.

Zolbetuximab is an anti-claudin18.2 (CLDN18.2) antibody, and the addition of zolbetuximab in combination with fluoropyrimidine and oxaliplatin as a first-line treatment for CLDN18.2-positive and HER2-negative gastric or gastroesophageal junction adenocarcinoma has been shown to improve survival. However, the efficacy and safety of the combination of zolbetuximab with combinations other than fluoropyrimidine and oxaliplatin have not been elucidated. The objective of the present study is to evaluate the feasibility of combination treatment with trifluridine/tipiracil (FTD/TPI), which is effective as a third- or later-line treatment, and zolbetuximab. In this study, 32 patients with CLDN18.2-positive and HER2-negative unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma who received two or more lines of chemotherapy will be recruited. The patients will receive FTD/TPI (35 mg/m2 twice daily on days 1-5 and days 8-12 every 4 weeks) plus zolbetuximab (an initial dose of 800 mg/m2 or 400 mg/m2 depending on prior zolbetuximab exposure, followed by 400 mg/m2 every 3 weeks). The primary endpoint is treatment-emergent events leading to the discontinuation of zolbetuximab. The secondary endpoints are the time to treatment failure, progression-free survival, overall survival, response rate, incidence of adverse events, and incidence of Grade 3 or higher adverse events. The results will be used to evaluate the feasibility of the treatment and are expected to be used to evaluate whether future trials can be conducted.