A Study of GSK5458514 Alone or With Other Cancer Drugs in Adults With Metastatic Castration-Resistant Prostate Cancer

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What is this study about?

This study involves people with metastatic castration-resistant prostate cancer, which is a type of prostate cancer that has spread to other parts of the body and continues to grow even when the amount of testosterone in the body is reduced to very low levels. The study will test a new medication called GSK5458514, which is designed to help the immune system fight cancer cells by targeting a protein called PSMA that is found on prostate cancer cells. This medication will be given either alone or together with other anti-cancer treatments. The medication is given through a vein as an infusion, which means it is delivered directly into the bloodstream over a period of time.

The purpose of the study is to find the best and safest dose of GSK5458514 and to check how well it is tolerated by participants. The study will look at any side effects that occur and will measure how the body processes the medication. Participants in this study will be men who have already received other treatments for their prostate cancer, including hormone therapy and chemotherapy with taxane-based medications, but whose cancer has continued to progress. The study will also check if the treatment helps to reduce the level of prostate-specific antigen, which is a substance in the blood that can indicate how the cancer is responding, and whether tumors shrink or stop growing.

During the study, participants will receive the medication and will be monitored closely through regular visits where doctors will perform physical examinations, blood tests, and imaging scans such as CT scans, MRI, or bone scans to see how the cancer is responding. The study will collect tissue samples from previous biopsies or may request a new biopsy to analyze the cancer cells and look for specific markers. Participants will need to continue their testosterone-lowering therapy throughout the study and must meet certain health requirements to be eligible. The study will track any side effects and changes in the cancer to understand how safe and effective GSK5458514 is for treating this type of prostate cancer.

1 Informed consent and screening

Before starting the study, your doctor will explain the study requirements and restrictions. You will need to sign an informed consent form, which confirms that you understand and agree to participate.

Your doctor will check that you meet the study requirements, including having adequate organ function and an ECOG performance status of 1 or less. The ECOG performance status is a scale that measures how the disease affects your daily living abilities, where 0 means you are fully active and 1 means you have some restrictions in physically strenuous activity.

Your testosterone level must be less than 50 ng/dL. If you have not had surgery to remove your testicles, you must continue taking medication to suppress testosterone production throughout the study. This medication must have been started at least 4 weeks before beginning the study treatment.

You will need to provide tissue samples from a previous biopsy or have a new biopsy taken. This tissue will be tested for PSMA, which is a protein found on prostate cancer cells, and other biological markers.

2 Step-up treatment period begins

The study treatment will begin on Day 1 of the step-up treatment period. Your performance status must not have worsened in the 2 weeks before this day.

You will receive GSK5458514, which is an experimental medication designed to help your immune system recognize and attack prostate cancer cells that have the PSMA protein.

The medication will be given to you through a vein as an infusion, which means it will be slowly delivered into your bloodstream over a period of time.

The medication comes as a powder that will be mixed into a solution before being given to you.

3 Dose escalation phase

During this phase, your doctor will determine the appropriate dose of GSK5458514 for you. The study is designed to find the maximum tolerated dose, which is the highest dose that can be given without causing unacceptable side effects.

Your doctor will closely monitor you for any dose limiting toxicities, which are serious side effects that occur during the observation period after receiving the medication.

The frequency and amount of GSK5458514 you receive will be determined by your doctor based on how you respond to the treatment and any side effects you experience.

4 Ongoing treatment and monitoring

You may receive GSK5458514 alone or in combination with other anti-cancer medications, depending on which part of the study you are in.

Your doctor will regularly check your blood to measure levels of PSA, which is a protein produced by prostate cells. A decrease in PSA levels can indicate that the treatment is working.

Your doctor will also perform imaging scans such as CT scans, MRI scans, or bone scans to check the size and spread of your cancer. These scans help determine your objective response rate, which measures whether the tumors have shrunk, stayed the same, or grown.

Blood samples will be taken to measure the amount of GSK5458514 in your bloodstream and to check for anti-drug antibodies, which are proteins your immune system might produce in response to the medication.

Your doctor will monitor you for any side effects throughout the treatment period. If you experience side effects, your dose may be adjusted or treatment may be paused.

5 Contraception requirements during treatment

During the study and for at least 195 days after your last dose of study medication, you must not donate sperm.

You must either abstain from sexual intercourse with women or use a condom during sexual intercourse. If your partner is a woman who can become pregnant, she should also use a highly effective method of birth control, as condoms can break or leak.

6 Follow-up after treatment

After completing the treatment phase, your doctor will continue to monitor your health and check for any long-term effects of the medication.

You will need to continue following the contraception requirements for at least 195 days after your last dose of GSK5458514.

Who Can Join the Study?

You must provide written permission to participate in the study after understanding all requirements and restrictions
Your organs such as liver, kidneys, and bone marrow must be working well enough
You must be a male participant who is 18 years of age or older
You must agree not to donate sperm during the study and for at least 195 days after the last dose of the study medicine
You must either avoid sexual intercourse with women as your usual lifestyle choice, or use a condom during sex and your female partner should also use a highly effective birth control method if she is able to become pregnant
You must have metastatic castration-resistant prostate cancer, which means prostate cancer that has spread to other parts of the body and continues to grow despite treatments that lower male hormones
Your prostate cancer diagnosis must be confirmed by examining tissue samples under a microscope, showing a type of cancer called adenocarcinoma
The spread of your cancer must be visible on imaging tests such as PET-CT scan, regular CT scan, MRI scan, or bone scan
Your cancer must meet specific criteria showing it is resistant to treatments that lower male hormones
You must have previously tried treatments targeting the male hormone receptor and these treatments did not work, and you must have also tried 1 or 2 chemotherapy treatments with drugs called taxanes
You must have either at least one area of cancer in soft tissues that can be measured, or rising levels of a protein called PSA in your blood on two separate tests at least one week apart with the most recent level being 2 or higher, or cancer in your bones shown by at least 2 spots on a bone scan
Your cancer must have gotten worse during your most recent treatment based on specific criteria
Your blood level of the male hormone testosterone must be very low, less than 50
You must have had surgery to remove both testicles, or be receiving continuous treatment with medications that lower male hormones, and this treatment must have started at least 4 weeks before joining the study and must continue throughout the study
Your ability to carry out daily activities must be good to fair, with no worsening in the 2 weeks before starting treatment
You must provide a sample of your cancer tissue, either from a new biopsy where a small piece of tissue is removed, or from stored tissue from a previous biopsy, so researchers can test for specific markers in your cancer

Who Cannot Join the Study?

Women cannot participate in this study, as it is only for male patients
Patients who are younger than the required age range cannot participate
Patients who are older than the allowed age range cannot participate
Patients who do not have metastatic castration-resistant prostate cancer, which means prostate cancer that has spread to other parts of the body and no longer responds to treatments that lower testosterone levels
Patients who belong to vulnerable population groups as defined by the study requirements cannot participate

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Institut Gustave Roussy	Villejuif	France
Hospital Universitario Hm Sanchinarro	Madrid	Spain

Other Sites

Site Name	City	Country
Hospital Universitario Fundacion Jimenez Diaz	Madrid	Spain
Hospital Universitario Quironsalud Madrid	Pozuelo De Alarcon	Spain
Hospital Hm Nou Delfos	Barcelona	Spain
Hospital Universitario Virgen De La Victoria	Malaga	Spain
Cujtiy Lsml Bioogj	Lyon	France
Hsveovuw Uzxdgxkoihjhu Dh Blfjvvy	Badajoz	Spain

Trial status

Country	Status	Recruitment Start
France	Recruiting	01.12.2025
Spain	Recruiting	01.12.2025

Trial locations

Investigated drugs:

GSK5458514

GSK5458514 is an investigational medication being tested in this study. It is a PSMA targeting T cell engager, which is a type of medicine designed to help the immune system find and attack prostate cancer cells. This medication works by connecting immune cells called T cells to cancer cells that have a specific protein called PSMA on their surface, which is commonly found on prostate cancer cells. The study will test this medication by itself and also in combination with other cancer treatments to see how well it works and how safe it is for people with advanced prostate cancer that has spread to other parts of the body and no longer responds to hormone therapy.

Investigated diseases:

Prostate cancer

Prostate Neoplasms – Prostate neoplasms are abnormal growths that develop in the prostate gland, a small walnut-shaped organ located below the bladder in men. These growths occur when cells in the prostate begin to multiply uncontrollably, forming a tumor. The condition can be either benign or malignant, with malignant forms having the potential to spread beyond the prostate. As the disease progresses, it may advance from a localized state to a more widespread condition affecting nearby tissues and potentially distant organs. In some cases, the disease becomes resistant to hormonal treatments that typically control prostate cell growth. Metastatic castration-resistant prostate cancer represents an advanced stage where the disease continues to progress despite treatments that lower male hormone levels in the body.

Trial ID:

2025-521581-10-00

Protocol code:

223050

NCT ID:

NCT06990880

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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A Study of GSK5458514 Alone or With Other Cancer Drugs in Adults With Metastatic Castration-Resistant Prostate Cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?