Claudin 18.2 is a promising therapeutic target overexpressed on the surface of gastric cancer cells. The addition of zolbetuximab, the monoclonal antibody targeting Claudin 18.2 to chemotherapy in two recent Phase 3 studies prolonged survival outcomes, indicating that Claudin 18.2 is a valid target in gastric cancer. Asan Medical Center researchers conducted a study on Claudin 18.2 expression in patients with operable gastric cancer and defined moderate to strong claudin expression in more than 75% of tumor cells as Claudin 18.2 overexpression, which was observed in 46.5% of patients with stage I-III tumors. This suggests that zolbetuximab-based treatment may be possible in patients with LAGC.
Therefore, The investigator designed a prospective, multicenter, open-label, Phase Ib/II study to determine the efficacy and safety of zolbetuximab/DOS as neoadjuvant chemotherapy in patients with LAGC.
Patients with newly diagnosed, pathologically confirmed, potentially resectable gastric or gastroesophageal junction adenocarcinoma
Subjects who are CLDN18.2 positive (VENTANA 43-14A ≥75%)
Patients with clinical stage T3-4/N0 or T2-4/N+ on CT according to the American Joint Committee on Cancer (AJCC) 8th edition
If suspected by CT, patient who has not been confirmed to have peritoneal seeding by laparoscopy
Patient who received investigational product in another clinical study 2 weeks prior to participation in this clinical study
Patient currently enrolled in another clinical study, other than the observational (non-interventional) study or follow-up period of an interventional clinical study.
Concomitant chemotherapy, immunotherapy, biologic or hormonal therapy. Hormonal therapies not related to treatment for cancer (e.g., hormone replacement therapy) are allowed.
Major surgical procedure within 28 days prior to zolbetuximab administration
Single group
zolbetuximab
Drug1. Neoadjuvant treatment : Zolbetuximab 800\*/600 mg/m2 Q3W on day (D) 1, Docetaxel 50 mg/m2 intravenously (IV) on D1, oxaliplatin 100 mg/m2 IV on D1, S-1 40 mg/m2 bid orally on D1-14, will be administered every three weeks for three cycles. (\*Loading dose of zolbetuximab (800 mg/m²) on C1D1, followed by subsequent doses of 600 mg/m² every 3 weeks) 2. Surgery : Total gastrectomy (TG) or distal gastrectomy (DG) accompanied with dissection of the D2 lymph node 3. Adjuvant treatment After 3-8 weeks from surgery, S-1 40/50/60 mg/m2 bid orally on D1-28 plus Zolbetuximab 600 mg/m2 on D1 and D22 will be administered every 6 weeks for 12 months as an adjuvant treatment.
Oxaliplatin
Drug1\. Neoadjuvant treatment : Zolbetuximab 800\*/600 mg/m2 Q3W on day (D) 1, Docetaxel 50 mg/m2 intravenously (IV) on D1, oxaliplatin 100 mg/m2 IV on D1, S-1 40 mg/m2 bid orally on D1-14, will be administered every three weeks for three cycles. (\*Loading dose of zolbetuximab (800 mg/m²) on C1D1, followed by subsequent doses of 600 mg/m² every 3 weeks) 2. Surgery : Total gastrectomy (TG) or distal gastrectomy (DG) accompanied with dissection of the D2 lymph node 3. Adjuvant treatment After 3-8 weeks from surgery, S-1 40/50/60 mg/m2 bid orally on D1-28 plus Zolbetuximab 600 mg/m2 on D1 and D22 will be administered every 6 weeks for 12 months as an adjuvant treatment.
Docetaxel
Drug1\. Neoadjuvant treatment : Zolbetuximab 800\*/600 mg/m2 Q3W on day (D) 1, Docetaxel 50 mg/m2 intravenously (IV) on D1, oxaliplatin 100 mg/m2 IV on D1, S-1 40 mg/m2 bid orally on D1-14, will be administered every three weeks for three cycles. (\*Loading dose of zolbetuximab (800 mg/m²) on C1D1, followed by subsequent doses of 600 mg/m² every 3 weeks) 2. Surgery : Total gastrectomy (TG) or distal gastrectomy (DG) accompanied with dissection of the D2 lymph node 3. Adjuvant treatment After 3-8 weeks from surgery, S-1 40/50/60 mg/m2 bid orally on D1-28 plus Zolbetuximab 600 mg/m2 on D1 and D22 will be administered every 6 weeks for 12 months as an adjuvant treatment.
S-1
Drug1\. Neoadjuvant treatment : Zolbetuximab 800\*/600 mg/m2 Q3W on day (D) 1, Docetaxel 50 mg/m2 intravenously (IV) on D1, oxaliplatin 100 mg/m2 IV on D1, S-1 40 mg/m2 bid orally on D1-14, will be administered every three weeks for three cycles. (\*Loading dose of zolbetuximab (800 mg/m²) on C1D1, followed by subsequent doses of 600 mg/m² every 3 weeks) 2. Surgery : Total gastrectomy (TG) or distal gastrectomy (DG) accompanied with dissection of the D2 lymph node 3. Adjuvant treatment After 3-8 weeks from surgery, S-1 40/50/60 mg/m2 bid orally on D1-28 plus Zolbetuximab 600 mg/m2 on D1 and D22 will be administered every 6 weeks for 12 months as an adjuvant treatment.
Evaluation of R0 resection rate in patients who underwent prior chemotherapy as a clinical trial.(phase II part)
Evaluation of R0 resection rate.
Recommended phase 2 dose (RP2D) (phase Ib part)
Recommended phase 2 dose (RP2D) (phase Ib part)
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