Phase II RAINSPOT: a multicentric open label trial of Zolbetuximab-Paclitaxel-Ramucirumab in second line setting for CLDN18.2 positive gastro-esophageal adenocarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

11 Dec 2025 → ongoing

Decision date (initial)

2025-09-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Astellas Pharma Global Development, Inc. (APGD)

External identifiers

EU CT number

2025-521358-41-00

ClinicalTrials.gov

NCT06962137

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To evaluate the effect of the addition of Zolbetuximab to standard treatment on survival in CLDN18.2 positive patients that were previously treated in first line but unexposed to Zolbetuximab or other anti CLDN18.2 targeted therapy.

Secondary objectives 5

1. Efficacy of the triple combination compared to retrospective data (Progression free survival; Best overall response)
2. Safety will be assessed continuously
3. Exploratory quality of life during treatment
4. Loss of CLDN18.2 positivity
5. Other exploratory biomarkers

Conditions and MedDRA coding

CLDN18.2 positive gastro-esophageal adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. At least 18 years of age at the time of signing the Informed Consent Form (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; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
9. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.

Exclusion criteria 7

1. Metastatic squamous cell cancer of the esophagus
2. Absolute contra-indication for anti-VEGF inhibitors (tumour 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is OS (overall survival), which is defined as the time from the date of signature of informed consent until death from any cause. Patients starting a subsequent line of treatment after study discontinuation will not be censored for survival at the start of this subsequent treatment. Subjects who are still alive at the time of analysis will be censored at the last day known to be alive.

Secondary endpoints 2

1. Secondary Endpoints PFS, which is defined as the time from the date of signature of informed consent until the date of radiological PD (per Response Evaluation Criteria in Solid Tumours [RECIST] 1.1) or death from any cause, whichever is earliest. Patients unprogressed at time of discontinuation for other causes, starting a subsequent line of treatment will be censored for progression at the start of this subsequent treatment.
2. Safety will be assessed and reported continuously as per regulations.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Filip Van Herpe

Public contact point

Organisation

UZ Leuven

Contact name

Filip Van Herpe

Third parties 2

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications