NCT06732856

A Phase Ib/II Trial of Neoadjuvant Zolbetuximab Plus Docetaxel, Oxaliplatin and S-1 Chemotherapy in Patients With Locally Advanced Gastric Cancer

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 57 (estimated)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Although the global incidence and mortality of gastric cancer has declined in recent decades, gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death. Surgical resection is the main treatment for patients with localized gastric cancer. However, postoperative recurrences are common, and approximately 40% of patients experience recurrences 2 years after surgery. Various adjuvant therapies have been studied over the past decades to improve the rate of postoperative recurrences. Perioperative chemotherapy and postoperative chemoradiotherapy or adjuvant chemotherapy has been shown to improve overall survival in patients with resectable gastric cancer. The preferred treatment strategy is chosen according to the expected locoregional control after surgery, and tends to vary depending on the geographical location. Two large randomized, controlled, Phase 3 trials in East Asia investigated the efficacy of S-1 for 1 year or capecitabine and oxaliplatin (XELOX) for 6 months as adjuvant chemotherapy following D2 gastrectomy compared to D2 gastrectomy alone in patients with resectable gastric cancer. Both studies showed an apparent benefit of adjuvant chemotherapy versus surgery alone in survival, with 5-year overall survival rates of 70 to 80% in patients receiving adjuvant chemotherapy and 60 to 70% in patients receiving surgery alone. Based on these results, D2 gastrectomy with S-1 or XELOX as adjuvant chemotherapy is the treatment strategy generally selected for patients with resectable gastric cancer in East Asia. However, approximately 30 to 35% of patients experience disease recurrence despite the addition of adjuvant chemotherapy, suggesting that a better treatment strategy needs to be developed in this clinical setting. One of the strategies for improving survival outcomes of locally advanced gastric cancer may be the introduction of neoadjuvant chemotherapy. Recently, the pivotal phase 3 PRODIGY and RESOLVE studies have demonstrated survival benefits of adding neoadjuvant chemotherapy to surgery followed by adjuvant chemotherapy over up-front surgery followed by adjuvant chemotherapy in Asian patients. Based on these results, neoadjuvant chemotherapy is considered one of the viable options for patients with locally advanced gastric cancer. 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. \< Primary objective(s)\> * RP2D (phase Ib part) * Pathologic complete regression rate (pCR) (phase II part) \< Secondary objective(s)\> * Progression-free survival by RECIST v1.1 * Overall survival (OS) * Overall response rate (ORR) during by RECIST v 1.1 * Disease control rate (DCR) by RECIST v 1.1 * Safety profiles by

Conditions

• Stomach Neoplasm
• Gastric (Stomach) Cancer

Interventions

Type	Name	Description
DRUG	zolbetuximab	1. 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.
DRUG	Oxaliplatin	1\. 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.
DRUG	Docetaxel	1\. 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.
DRUG	S-1	1\. 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.

Timeline

• Start date: 2025-04-04
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2024-12-13
• Last updated: 2025-07-28

Locations

2 sites across 1 country: South Korea