A Phase Ib/II Trial of Neoadjuvant Zolbetuximab Plus Docetaxel, Oxaliplatin and S-1 Chemotherapy in 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.
• 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
• Subject able to provide signed informed consent form, including compliance with the requirements and contraindications specified in the informed consent form (ICF) and in this protocol
• Patients aged 19 years or older at study entry
• Patient with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Patient with expected survival \>12 months
• Weight \>30 kg
⁃ Patient without neuropathy A. Grade 1 is allowed based on NCI CTCAE v5.0. B. Grade 2 or higher is excluded based on NCI CTCAE v5.0
⁃ Individual with confirmed adequate normal organ and bone marrow function, as defined in the applicable items below:
∙ Hemoglobin ≥9.0 g/dL
‣ Absolute neutrophil count (ANC) \>1.5 x 103/mcL (\>1,500 per mm3)
‣ Platelet count ≥100 x 109/L
‣ Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)
‣ AST (SGOT)/ALT (SGPT) ≤2.5 x institutional ULN
‣ Measured creatinine clearance (CL) \>40 mL/min or creatinine CL \>40 mL/min as calculated by Cockcroft-Gault formula (Cockcroft and Gault 1976) or based on a 24-hour urine sample for determination of creatinine clearance
⁃ Male creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x Serum creatinine (mg/dL)
• Female creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x Serum creatinine (mg/dL) x 0.85
⁃ Evidence of menopause, or negative urine/blood pregnancy test in premenopausal women; women with amenorrhea for at least 12 months without any other medical cause are considered menopausal. The following age requirements apply:
∙ A woman under age 50 is considered menopausal if 1) she has had amenorrhea for at least 12 months without hormone therapy, and 2) her LH and FSH blood levels are at menopausal levels or she has undergone bilateral oophorectomy, hysterectomy, etc.
‣ A woman aged 50 years or older is considered menopausal if
⁃ she has had amenorrhea for at least 12 months without hormone therapy, or
• she became menopause after 1 year of amenorrhea following radiation or anticancer treatment, or
• she has undergone bilateral oophorectomy, bilateral salpingectomy, hysterectomy, etc.
⁃ Patient who is willing and able to comply with the protocol during the study, including treatments and tests such as scheduled visits, follow-up, etc.