A Study of CLDN6 CAR-T Cell Therapy With or Without CLDN6 RNA-LPX Vaccine in Patients With CLDN6-Positive Advanced Solid Tumors That Returned or Did Not Respond to Treatment

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What is this study about?

This study involves patients with solid tumors, which are cancers that form in organs and tissues of the body. The study is examining patients whose cancer has either come back after previous treatment or has not responded to earlier treatments. The treatment being tested is called BNT211, which is a type of cell therapy that uses specially modified immune cells from the patient’s own body. These cells are engineered to recognize and attack cancer cells that have a specific protein called CLDN6 on their surface. In some parts of the study, patients will receive this cell therapy alone, while in other parts, patients will receive the cell therapy together with a vaccine made from genetic material that may help the immune system work better against the cancer.

The purpose of the study is to find out if this treatment is safe and to determine the best dose that patients can tolerate. The study will also look at whether the treatment helps to control or shrink the tumors. Patients in this study must have tumors that show the presence of the CLDN6 protein and must have cancer that has spread or cannot be removed by surgery. The treatment is given through an infusion into a vein. During the study, doctors will closely monitor patients for any side effects and will measure how the tumors respond to the treatment using imaging scans or blood tests that measure certain markers in the blood.

The study will follow patients for several years to understand the long-term effects of the treatment and how well it works over time. Doctors will collect blood samples to measure changes in the immune system and to see how long the modified immune cells stay in the body. The study will test different doses of the cell therapy and the vaccine to find the most appropriate amount to use in future studies. Some patients will receive treatment made using a manual process while others will receive treatment made using an automated process to compare whether both methods work similarly.

1 Tumor tissue evaluation

Your tumor tissue will be tested to confirm that it expresses a specific protein called CLDN6. This test uses a laboratory method called immunohistochemistry, which identifies proteins in tissue samples.

To qualify for this study, at least 50% of your tumor cells must show the presence of CLDN6 protein at a certain level of intensity.

2 Disease measurement and baseline assessment

Your disease will be measured using imaging scans to establish a baseline. This measurement follows a standard system called RECIST 1.1, which is a set of rules for measuring tumors.

If you have certain tumor types such as germ cell tumors or ovarian cancer, your disease may be evaluated using blood tests that measure specific markers such as CA-125, AFP, or beta-hCG instead of imaging alone.

These baseline measurements will be used to compare changes in your disease throughout the study.

3 Blood collection for cell therapy preparation

Your blood will be collected through a process that allows specific immune cells called T cells to be separated from your blood. These cells will be sent to a laboratory.

In the laboratory, your T cells will be modified to recognize and attack tumor cells that express the CLDN6 protein. This modified cell product is called CLDN6 CAR-T.

The preparation of your personalized cell therapy will take several weeks.

4 Conditioning chemotherapy

Before receiving the modified cells, you may receive chemotherapy to prepare your body. This is called conditioning chemotherapy or lymphodepletion.

This chemotherapy helps reduce the number of existing immune cells in your body, which allows the modified CAR-T cells to expand and work more effectively.

5 CLDN6 CAR-T cell infusion

You will receive your modified T cells through an intravenous infusion, which means the cells will be given directly into your vein.

The product name is BNT211, and it is provided as a dispersion for infusion.

The dose of CLDN6 CAR-T cells you receive will depend on which dose level is being tested in the study. The study is designed to find the highest safe dose.

This infusion is given as a single dose on one day.

6 Optional RNA-based vaccine administration

Depending on which part of the study you are in, you may also receive an investigational vaccine called CLDN6 RNA-LPX (also known as RBP030.2).

This vaccine is designed to help boost the activity of the CAR-T cells by stimulating your immune system to better recognize the CLDN6 protein on tumor cells.

The vaccine is given through an intravenous infusion into your vein.

If you receive this vaccine, it will be given multiple times according to a specific schedule determined by the study protocol.

7 Monitoring period for immediate side effects

After receiving the CAR-T cells, you will be closely monitored for a specific period called the dose-limiting toxicity evaluation period.

During this time, the medical team will watch for any serious side effects that might occur as a result of the treatment.

This monitoring helps determine whether the dose you received is safe and tolerable.

8 Ongoing safety monitoring

Throughout the study, you will be monitored for any side effects related to the treatment. These are called treatment-emergent adverse events.

Special attention will be given to side effects that are severe (Grade 3 or higher), serious, or life-threatening.

Blood samples will be taken regularly to measure cytokines, which are proteins in your blood that indicate how your immune system is responding to the treatment.

The levels and patterns of these immune factors will be tracked over time to understand how the treatment affects your immune system.

9 Disease response evaluation

Your tumor will be regularly assessed using imaging scans to see how it responds to the treatment.

The response will be classified according to standard criteria as complete response (tumor completely disappears), partial response (tumor shrinks significantly), stable disease (tumor neither grows nor shrinks significantly), or progressive disease (tumor grows).

For certain tumor types, blood tests measuring tumor markers may be used instead of or in addition to imaging scans.

The first assessment of stable disease will occur at least 6 weeks after your first dose of treatment.

10 Long-term follow-up

You will continue to be followed over an extended period to monitor the duration of any response to treatment and your overall health.

If your tumor responds to treatment, the time from when the response is first observed until the tumor grows again or until death will be recorded. This is called duration of response.

Long-term safety information will continue to be collected throughout your participation in the study.

Who Can Join the Study?

Requirements to join this clinical trial:

You must have a tumor that tests positive for a protein called CLDN6. This means that at least half of your tumor cells must show this protein at a certain level when examined under a microscope using a special test called immunohistochemistry, which is a laboratory method to detect specific proteins in tissue samples.
You must have a tumor that can be measured. This is usually done through imaging scans following specific guidelines called RECIST 1.1. For certain cancer types like germ cell tumors or ovarian cancer, measurement can be done using blood tests that check for specific markers such as CA-125, AFP, or beta-hCG. These markers are substances in your blood that can indicate the presence or activity of cancer. The level of these markers must be at least twice the normal upper limit before treatment starts.
You must have a solid tumor, which is a type of cancer that forms a mass or lump, rather than blood cancers. This tumor must be either metastatic, meaning it has spread to other parts of your body, or unresectable, meaning it cannot be removed by surgery. Additionally, there must be no standard treatment available that is likely to help you, or you must not be suitable for such treatments.
Both male and female patients can participate in this trial.
Adults and elderly patients can participate in this trial.

Who Cannot Join the Study?

The study does not list specific exclusion criteria in the provided information, which means the detailed reasons why patients cannot participate are not available in this document.
Generally, clinical trials have exclusion criteria to ensure patient safety and study accuracy, but these specific details would need to be obtained from the complete study documentation.
Patients interested in participating should discuss their individual medical situation with their healthcare provider to determine if they might be suitable for this study.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Medizinische Hochschule Hannover	Hanover	Germany
Center For Pediatric And Adolescent Medicine Of The Johannes Gutenberg University Mainz	Mainz	Germany
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany

Other Sites

Site Name	City	Country
Netherlands Cancer Institute	Amsterdam	The Netherlands
Region Stockholm – SLSO	Stockholm	Sweden
Universitaetsklinikum Regensburg AöR	Regensburg	Germany
Universitaetsklinikum Erlangen AöR	Erlangen	Germany
Charite Universitaetsmedizin Berlin KöR	Berlin	Germany
Umglzkuwsj Mntjxzt Cfqztl Hyahwuwvyeovzfvtm	Hamburg	Germany
Uhepsikudr Hsagnzkm Cthyrsd	Cologne	Germany
Euepzpg Uqxgcwxftgsc Mxlghqe Cslydky Rfvxzhaon (azbtynq Msi	Rotterdam	The Netherlands

Trial status

Country	Status	Recruitment Start
Germany	Recruiting	01.06.2020
Sweden	Recruiting	01.06.2020
The Netherlands	Recruiting	01.06.2020

Trial locations

CLDN6 CAR-T is a treatment made from your own immune cells called T cells. These cells are collected from your blood and modified in a laboratory to recognize and attack cancer cells that have a specific protein called CLDN6 on their surface. After modification, these cells are given back to you through an infusion to help fight your cancer.

CLDN6 RNA-LPX is a vaccine that contains genetic material wrapped in tiny fat particles called liposomes. This vaccine is designed to help your immune system better recognize cancer cells that have the CLDN6 protein. It works by training your body to produce an immune response against tumors with this protein marker.

Investigated diseases:

Solid Tumors – Solid tumors are abnormal masses of tissue that develop when cells in the body grow and divide uncontrollably. Unlike liquid cancers that affect blood and lymph systems, these tumors form solid lumps in organs or tissues throughout the body. They can occur in various locations including the breast, lung, colon, prostate, and many other organs. As the tumor grows, it can interfere with the normal function of the affected organ or tissue. The abnormal cells may remain localized in one area or can spread to nearby tissues and other parts of the body through blood vessels or the lymphatic system. Solid tumors are classified based on their location, the type of cells they originate from, and their behavior patterns.

Trial ID:

2024-514962-38-00

Protocol code:

BNT211-01

NCT ID:

NCT04503278

Trial Phase:

Human Pharmacology (Phase I) – First administration to humans

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A Study of CLDN6 CAR-T Cell Therapy With or Without CLDN6 RNA-LPX Vaccine in Patients With CLDN6-Positive Advanced Solid Tumors That Returned or Did Not Respond to Treatment

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?