Zolbetuximab with chemotherapy for HER2-negative, Claudin 18.2–positive metastatic gastric or gastroesophageal junction adenocarcinoma
Real-WorlD ZolbetUximab Combined With chemotheraPy in Patients With HER-2 Negative and CLaudin 18.2 PosItive MetastatiC GAsTric or Gastroesophageal Junction AdEnocarcinoma
This project will try zolbetuximab together with FOLFOX or XELOX as first-line treatment for adults whose HER2-negative stomach or gastroesophageal junction cancers strongly express Claudin 18.2.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 70 (estimated) |
| Ages | 18 Years to 100 Years |
| Sex | All |
| Sponsor | European Institute of Oncology Academic / other |
| Drugs / interventions | Zolbetuximab, chemotherapy, immunotherapy |
| Locations | 1 site (Milan) |
| Trial ID | NCT07427992 on ClinicalTrials.gov |
What this trial studies
This national prospective real-world observational program will collect efficacy and safety data on adults with locally advanced, unresectable or metastatic HER2-negative, Claudin 18.2–positive gastric or gastroesophageal junction adenocarcinoma treated with zolbetuximab plus fluoropyrimidine/platinum chemotherapy (FOLFOX or XELOX). Eligible patients must have tumors with ≥75% Claudin 18.2 membranous staining and ECOG performance status 0–1 and can be enrolled when starting or already receiving the combination via the Early Access Program or local reimbursement. Pre-planned subgroup analyses will address practical clinical questions not fully explored in randomized trials and compare real-world outcomes with the phase III evidence base. Clinical and safety data will be collected at participating centers with local or central pathology confirmation.
Who should consider this trial
Good fit: Adults with histologically confirmed, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma that is HER2-negative, shows ≥75% moderate-to-strong membranous Claudin 18.2 staining, has ECOG 0–1, and can access zolbetuximab through the Early Access Program or local reimbursement are ideal candidates.
Not a fit: Patients whose tumors lack significant Claudin 18.2 expression, who are HER2-positive, who have ECOG ≥2, or who have already received prior systemic therapy are unlikely to benefit from this first-line program.
Why it matters
Potential benefit: If successful, this work could confirm that adding zolbetuximab to standard first-line chemotherapy improves outcomes for patients with Claudin 18.2–positive tumors in routine care.
How similar studies have performed: Two phase III randomized trials (SPOTLIGHT and GLOW) demonstrated benefit for zolbetuximab in this setting and led to regulatory approval for first-line use.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patient with histologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma. * Patient with locally advanced, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. * Patient whose tumor expresses claudin18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining as determined by local or central immunohistochemistry testing. * Patient with a Human epidermal growth factor receptor 2 negative tumor by local testing on a gastric or gastroesophageal junction tumor specimen. * Patient with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Patient who can have access to the Zolbetuximab EAP program or locally authorized and reimbursed (AIFA) procedure. * Patient who has about to start first-line Zolbetuximab + FOLFOX/XELOX or who has an ongoing Zolbetuximab FOLFOX/XELOX with available clinical data. Exclusion Criteria: * Patient has previously received treatment in a clinical trial of zolbetuximab, or a clinical trial that included zolbetuximab as 1 of the treatment options, even if the patient was not given zolbetuximab. * Patient has known dihydropyrimidine dehydrogenase deficiency. * Patient has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. However, patient may have received either neoadjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies as long as it was completed at least 6 months prior to participation.
Where this trial is running
Milan
- European Institute of Oncology — Milan, Italy (Recruiting)
Study contacts
- Study coordinator: Chiara Alessandra Cella, MD
- Email: divisione.gastrointestinale@ieo.it
- Phone: 00390257489258
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.