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

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.

Conditions

• Stomach Neoplasm
• Gastric (Stomach) Cancer

Interventions

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.

Sponsors & Collaborators

• Asan Medical Center

  lead OTHER

Principal Investigators

• Min-Hee Ryu, MD, PhD · Asan Medical Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-04-04

Primary Completion

2027-12-31

Completion

2027-12-31

Countries

• South Korea

Study Locations