A Study of Eciskafusp Alfa and Bacillus Calmette-Guérin (BCG) in Participants with BGC-Unresponsive High-Risk Bladder Cancer

1. Why is this study needed?

Every year, more than half a million people around the world are diagnosed with bladder cancer. About three-quarters of these cases are a type called non-muscle invasive bladder cancer, or a cancer that is contained within the outer wall of bladder without reaching the muscle layer underneath (known as NMIBC). Among these, approximately half are considered to have a so called high-risk of getting worse. Typically, high-risk NMIBC is treated by removing the tumor from the bladder and then using a treatment that involves a bacteria called Bacillus Calmette-Guérin (BCG). This treatment works well for about 70% of patients, but many patients either do not respond to BCG or cannot tolerate it. Even for those who do respond initially, the cancer often comes back, with more than half of the patients experiencing a recurrence within five years. As such, there are few treatment options available if BCG treatment fails. This is called “BCG-unresponsive”.

This study is testing a medicine called eciskafusp alfa in combination with BCG in people with BCG-unresponsive high-risk NMIBC. It is being developed to treat BCG-unresponsive high-risk NMIBC.

Eciskafusp alfa is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved eciskafusp alfa (in combination with BCG) for the treatment of bladder cancer.

This study aims to test how safe eciskafusp alfa (at different doses) in combination with BCG, if it works in people with bladder cancer and to understand what happens to eciskafusp alfa once it is in the body. Based on how the combination treatment of eciskafusp alfa and BCG works, other patients might later receive only eciskafusp alfa.

2. Who can take part in the study?

People aged 18 years and older with a certain type of bladder cancer (known as BCG-unresponsive high-risk NMIBC) can take part in this study if are ineligible or have decided not to get standard treatment (surgery to remove the bladder).

People may not be able to take part in this study if they have certain ongoing medical conditions, or are pregnant or currently breastfeeding. Participants who are planning to become pregnant during or shortly after the trial are not able to participate.

3. How does this study work?

People will be examined to check if they are able to participate in the study. The examination period will take place from 1 to 21 days before the start of treatment. Everyone who joins this study will be given eciskafusp alfa with or without BCG (depending on when they are joining the study) via a small tube in the bladder for two years at different intervals. This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given. During this study, the study doctor will see the participants regularly to check if the treatment is working and if participants have any unwanted effects from the treatment.

Participants will have follow-up visits during 1 year after completing the study treatment, during which the study doctor will check on the participant’s wellbeing.

Total time of participation in the study will be about 3 years.

Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. What are the main results measured in this study?

The main purpose of the study is to check if the treatment with eciskafusp alfa and BCG is safe. This is done by measuring the number and seriousness of any unwanted effects that may occur after receiving the study treatment and up to 1 year after completing the treatment.

Other key results measured in the study include:

• The highest dose of eciskafusp alfa that can be given to participants before they experience any unacceptable, unwanted side effects.
• The eciskafusp alfa dose that provides the most benefits, if any.
• What happens to eciskafusp alfa at different doses in the body, starting with the first study treatment until completion of study treatment.
• If it works in people with non-muscle invasive bladder cancer

5. Are there any risks or benefits in taking part in this study?

It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally compared to those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

Risks associated with the study drugs

Participants may have unwanted effects of the medicines used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

Participants will be told about the known unwanted effects of eciskafusp alfa and BCG, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Potential unwanted effects of eciskafusp alfa to the organs and systems of the body that are involved in reproduction and the production and excretion of urine cannot be excluded in participants. The most common problem after bladder treatment with BCG is irritation that affects the lower part of the urinary system, causing symptoms like frequent urination and a burning feeling.

The study medicines may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.

Benefits associated with the study drugs

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future.