Phase II RAINSPOT: Zolbetuximab-Paclitaxel-Ramucirumab for CLDN18.2 Positive Gastro-esophageal Cancer

Universitaire Ziekenhuizen KU Leuven

Status and phase: Begins enrollment in 4 months; Phase 2

Conditions: Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma; Gastric Cancer Adenocarcinoma Metastatic

Treatments: Drug: zolbetuximab; Other: Retrospective cohort, no intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT06962137

2025-521358-41-00 (EU Trial (CTIS) Number)

ISR007148 (Other Grant/Funding Number)

S70358

Details and patient eligibility

About

This study examines whether adding the drug Zolbetuximab to an existing treatment (Paclitaxel and Ramucirumab) can improve patients' survival. The goal is to see if this combination works better for patients whose tumours contain a specific protein (CLDN18.2). The results will be compared to past patient data from those who only received the standard treatment.

Zolbetuximab (Vyloy) is a cancer medicine that is used to treat adults with gastric or gastro-esophageal junction adenocarcinoma (a type of cancer of the stomach or the transition between the stomach and esophagus). Zolbetuximab will be administered via an intravenous infusion in combination with Paclitaxel and Ramucirumab (Cyramza) (two other cancer drugs that are the standard treatment for this condition). Treatment will take place at regular intervals in the hospital. In addition to treatment,patients will undergo a tumour biopsy. While the biopsy procedure may cause some discomfort or pain, it will only be performed if medically justifiable. Patients participation in the study will continue as long as they receive treatment and the disease does not worsen. The overall duration of the study, for all patients, will span several years.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Prospective cohort - Zolbetuximab + SOC Palcitaxel and Ramucirumab

Experimental group

Description:

* Zolbetuximab: 800 mg/m² loading dose of at C1D1, followed by subsequent doses of 400 mg/m² every 2 weeks. Zolbetuximab should be administered after antiemetic premedication but prior to Paclitaxel-Ramucirumab. * Paclitaxel: 80 mg/m² weekly for 3 weeks followed by a week of break according to routine practice. * Ramucirumab: 8 mg/kg every 2 weeks according to routine practice.

Treatment:

Drug: zolbetuximab

Retrospective cohort

Other group

Description:

For the retrospective cohort the investigators will identify patients treated with Paclitaxel-Ramucirumab between January 2021 until December 2023 (the era of immunotherapy) in the forementioned centers that have confirmed CLDN18.2 positivity on a baseline biopsy but were not treated with Zolbetuximab in first line setting (nor in experimental setting). Treatment with immunotherapy or targeted therapy in first line setting is allowed.

Treatment:

Other: Retrospective cohort, no intervention