Neoadjuvant zolbetuximab with docetaxel, oxaliplatin and S-1 for locally advanced stomach cancer
A Phase Ib/II Trial of Neoadjuvant Zolbetuximab Plus Docetaxel, Oxaliplatin and S-1 Chemotherapy in Patients With Locally Advanced Gastric Cancer
This study will test whether adding zolbetuximab to docetaxel, oxaliplatin, and S-1 before surgery helps people with locally advanced, CLDN18.2-positive stomach cancer shrink tumors and have better outcomes.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 57 (estimated) |
| Ages | 19 Years and up |
| Sex | All |
| Sponsor | Asan Medical Center Academic / other |
| Drugs / interventions | zolbetuximab, chemotherapy, immunotherapy, radiation |
| Locations | 2 sites (Seoul and 1 other locations) |
| Trial ID | NCT06732856 on ClinicalTrials.gov |
What this trial studies
This is a prospective, multicenter, open-label Phase Ib/II study of zolbetuximab combined with docetaxel, oxaliplatin and S-1 (DOS) given before surgery for patients with locally advanced gastric or gastroesophageal junction adenocarcinoma that overexpresses Claudin 18.2 (VENTANA 43-14A ≥75%). Phase Ib focuses on safety and tolerability of the neoadjuvant combination and Phase II examines efficacy signals such as pathological response and resection rates. Patients will be staged by CT (and laparoscopy if peritoneal disease is suspected) and receive the zolbetuximab+DOS regimen prior to planned gastrectomy with D2 lymphadenectomy. Key outcomes include safety, pathological tumor response, R0 resection rate, recurrence-free survival, and overall survival.
Who should consider this trial
Good fit: Adults (≥19) with newly diagnosed, potentially resectable gastric or gastroesophageal junction adenocarcinoma that is CLDN18.2-positive (VENTANA 43-14A ≥75%), clinical stage T3-4 or T2-4/N+, ECOG 0–1, weight >30 kg, and without grade ≥2 neuropathy are the intended candidates.
Not a fit: Patients who are CLDN18.2-negative, have widespread distant metastases beyond limited lymph nodes, poor performance status (ECOG ≥2), significant neuropathy, prior incompatible therapies, or non-adenocarcinoma histology are unlikely to benefit from this neoadjuvant approach.
Why it matters
Potential benefit: If successful, adding zolbetuximab could increase tumor shrinkage before surgery, improve complete resection rates, and reduce recurrence risk for CLDN18.2-positive patients.
How similar studies have performed: Large Phase 3 trials adding zolbetuximab to chemotherapy in advanced gastric cancer have improved survival and validate Claudin 18.2 as a target, but applying zolbetuximab specifically as neoadjuvant therapy in resectable locally advanced disease is less established.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Patients with newly diagnosed, pathologically confirmed, potentially resectable gastric or gastroesophageal junction adenocarcinoma
2. Subjects who are CLDN18.2 positive (VENTANA 43-14A ≥75%)
3. Patients with clinical stage T3-4/N0 or T2-4/N+ on CT according to the American Joint Committee on Cancer (AJCC) 8th edition
4. If suspected by CT, patient who has not been confirmed to have peritoneal seeding by laparoscopy
5. 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
6. Patients aged 19 years or older at study entry
7. Patient with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
8. Patient with expected survival \>12 months
9. Weight \>30 kg
10. 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
11. 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
1. Male creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x Serum creatinine (mg/dL)
2. Female creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x Serum creatinine (mg/dL) x 0.85
12. 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
1. she has had amenorrhea for at least 12 months without hormone therapy, or
2. she became menopause after 1 year of amenorrhea following radiation or anticancer treatment, or
3. she has undergone bilateral oophorectomy, bilateral salpingectomy, hysterectomy, etc.
13. 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.
Exclusion Criteria:
1. Patient who received investigational product in another clinical study 2 weeks prior to participation in this clinical study
2. Patient currently enrolled in another clinical study, other than the observational (non-interventional) study or follow-up period of an interventional clinical study.
3. Concomitant chemotherapy, immunotherapy, biologic or hormonal therapy. Hormonal therapies not related to treatment for cancer (e.g., hormone replacement therapy) are allowed.
4. Major surgical procedure within 28 days prior to zolbetuximab administration
5. Distant metastasis including M1 lymph node
6. Patient unable to take oral medication
7. Gastric outlet obstruction and/or severe gastrointestinal hemorrhage that restricts diet without treatment
8. Impaired intestinal absorption, including:
* Intestinal obstruction
* Chronic inflammatory bowel disease
* Operation history of extended bowel resection
* Gastric dumping syndrome
9. Patient with a history of organ transplant
10. Uncontrolled intercurrent disease including, but not limited to:
Ongoing or active infection, congestive heart failure with symptoms, uncontrolled hypertension, unstable angina, arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions accompanied with diarrhea, mental illness or social conditions that prevent compliance with study requirements, significantly increase the risk of adverse reactions, or interfere with written consent
11. History of other primary malignancy, with the exception of:
* Patient who is at low risk of recurrence with disease-free status for at least 5 years prior to starting chemotherapy due to curative treatment
* Patient who is currently disease-free with cured skin cancer (except melanoma) or lentigo maligna
* Patient who is currently disease-free with cured in situ carcinoma
12. Patient with a history of active congenital immunodeficiency
13. Active infection, such as tuberculosis, confirmed by history, physical examination, radiographic findings, and TB testing per local standards, or HIV.
* Tuberculosis: History, physical examination, or radiological findings suggestive of active tuberculosis, or tuberculosis confirmed by tuberculosis testing per local standards (active TB is excluded and old TB is allowed)
* For HBV infection, the patient may be enrolled if appropriately treated with antiviral agents, etc.
* HIV
1. HIV Ag/Ab: If reactive, exclude
2. HIV Ag/Ab: If non-reactive, enroll
14. Pregnant or lactating woman and man or woman of childbearing potential who is unwilling to use effective contraception (from the screening period to 90 days after the last dose of zolbetuximab)
15. Individual with known allergy and hypersensitivity to the investigational product or its components
Where this trial is running
Seoul and 1 other locations
- Asan Medical Center — Seoul, South Korea (Recruiting)
- Asan Medical Center — Seoul, South Korea (Recruiting)
Study contacts
- Principal investigator: Min-Hee Ryu, MD, PhD — Asan Medical Center
- Study coordinator: Min-Hee Ryu, MD,PhD
- Email: miniryu@amc.seoul.kr
- Phone: 82-2-3010-5935
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.