Zolbetuximab with paclitaxel and ramucirumab for CLDN18.2-positive stomach and gastro‑esophageal junction cancer
Phase II RAINSPOT: a Multicentric Open Label Trial of Zolbetuximab-Paclitaxel-Ramucirumab in Second Line Setting for CLDN18.2 Positive Gastro-esophageal Adenocarcinoma
This treatment tests whether adding zolbetuximab to paclitaxel and ramucirumab helps adults with metastatic gastro‑esophageal adenocarcinoma whose tumors are CLDN18.2‑positive live longer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 100 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Universitaire Ziekenhuizen KU Leuven Academic / other |
| Drugs / interventions | Zolbetuximab, immunotherapy, Ramucirumab |
| Locations | 6 sites (Antwerp and 5 other locations) |
| Trial ID | NCT06962137 on ClinicalTrials.gov |
What this trial studies
This Phase II trial gives zolbetuximab by IV together with standard paclitaxel and ramucirumab to adults with metastatic gastric or gastro‑esophageal junction adenocarcinoma who have already received one prior standard first‑line therapy. Patients must have tumors that are CLDN18.2‑positive by a specified immunohistochemistry assay and will undergo tumor biopsy and regular clinical and imaging follow‑up. Outcomes for the treated group will be compared to historical (retrospective) cohorts of patients who received paclitaxel and ramucirumab alone. Treatment is given at scheduled hospital visits and safety, response, and survival endpoints will be recorded.
Who should consider this trial
Good fit: Adults (≥18 years) with metastatic gastric or gastro‑esophageal junction adenocarcinoma, WHO/ECOG performance status 0–1, progression after one prior first‑line therapy, and tumors showing CLDN18.2 expression in ≥75% of cells at moderate‑to‑strong intensity are ideal candidates.
Not a fit: Patients without CLDN18.2 expression, with squamous esophageal cancers, poor performance status, or absolute contraindications to anti‑VEGF therapy are unlikely to benefit from this regimen.
Why it matters
Potential benefit: If successful, this combination could extend survival or improve outcomes for patients with CLDN18.2‑positive metastatic gastro‑esophageal adenocarcinoma.
How similar studies have performed: Previous clinical trials of zolbetuximab combined with chemotherapy in CLDN18.2‑positive gastric/GEJ cancer have shown promising improvements in outcomes, supporting further testing in this setting.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. At least 18 years of age at the time of ICF 2. WHO performance status 0 - 1 3. Histologically proven metastatic gastroesophageal adenocarcinoma 4. Pretreatment with one 1st line therapy according to SOC (+/- immunotherapy) 5. If relapse while adjuvant (immune/chemo) therapy or within 6 months ending adjuvant therapy the adjuvant therapy is considered a first line therapy 6. CLDN18.2-positive (defined as ≥75% of tumour cells showing moderate-to-strong membranous CLDN18.2 staining, as determined by immunohistochemistry using the VENTANA CLDN18 \[43-14A\] RxDx Assay. 7. Any PDL1 score 8. Use of highly effective methods of birth control 9. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures. Exclusion Criteria: \- 1. Metastatic squamous cell cancer of the esophagus 2. Absolute contra-indication for anti-VEGF inhibitors (tumor perforation, active proteinuria, recent stroke, myocardial infarction, acute arterial thrombosis, active wound problem) 3. Other active malignancy 4. Pretreatment with Zolbetuximab or other anti-CLDN18.2 direct therapy in first line setting once available. 5\. Known hypersensitivity to the active substance Zolbetuximab or to any of the excipients \[(Arginine, Phosphoric acid (E 338), Sucrose, Polysorbate 80 (E 433)\] 6. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive 7. Participation in another interventional Trial with an investigational medicinal product (IMP) or device
Where this trial is running
Antwerp and 5 other locations
- Uza — Antwerp, Belgium (Not_yet_recruiting)
- Cliniques Universitaires Saint-Luc Brussels — Brussels, Belgium (Not_yet_recruiting)
- Hub — Brussels, Belgium (Not_yet_recruiting)
- UZ Gent — Ghent, Belgium (Not_yet_recruiting)
- UZ Leuven — Leuven, Belgium (Recruiting)
- AZ Delta Roeselare — Roeselare, Belgium (Not_yet_recruiting)
Study contacts
- Principal investigator: Filip Van Herpe, MD — Universitaire Ziekenhuizen KU Leuven
- Study coordinator: Filip Van Herpe, MD
- Email: filip.vanherpe@uzleuven.be
- Phone: +32 16 34 42 18
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.