A Study of GSK4524101 and Niraparib for Adults with Advanced Solid Tumors or Metastatic Breast Cancer with BRCA Gene Changes

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What is this study about?

This study involves people with different types of solid tumors, which are cancers that form solid masses rather than blood cancers. The first part of the study will include people with advanced or metastatic solid tumors, which means the cancer has spread to other parts of the body, and who have tried all available standard treatments without success. The second part of the study will focus specifically on people with metastatic breast cancer that has a gBRCAmut (a specific inherited change in the BRCA gene), is HER2-negative or HER2-low (meaning the cancer has little or no HER2 protein), and who have received no more than three previous treatment plans. The study will test two medications: GSK4524101, which is an experimental drug that works by blocking an enzyme called DNA Polymerase Theta, and niraparib, which is a PARP inhibitor that prevents cancer cells from repairing their damaged genetic material. Both medications are taken by mouth as tablets.

The purpose of the study is to find out what dose of GSK4524101 can be given safely, either alone or together with niraparib, and to see if the combination of these two drugs can help slow down or stop the growth of cancer. The study is divided into two parts. In the first part, small groups of people will receive increasing doses of GSK4524101 alone or combined with niraparib to find the highest dose that can be given without causing serious side effects. This part will also include a group to test whether taking GSK4524101 with food affects how the body processes the medication. In the second part, a larger group of people with the specific type of breast cancer described above will receive the combination of GSK4524101 and niraparib at a dose determined to be safe from the first part, to learn more about whether this combination can help shrink tumors.

Throughout the study, participants will have regular check-ups where doctors will monitor for any side effects and take blood samples to measure the amount of medication in the body. The study will also assess how well the treatment works by looking at whether tumors shrink or stop growing, and how long any positive effects last. Participants in the first part will help determine the safest dose to use, while those in the second part will help show whether the combination treatment can provide benefit for people with this specific type of breast cancer who have not previously received a PARP inhibitor.

1 Initial treatment phase

The study is divided into two parts. The part assigned to you will depend on your specific medical condition and treatment history.

If you are assigned to Part 1, you will receive GSK4524101 either alone or in combination with niraparib. GSK4524101 is an investigational medication that works by blocking a protein called DNA Polymerase Theta. Niraparib is a medication that blocks another protein called PARP. Both medications are taken by mouth as tablets.

If you are assigned to Part 2, you will receive GSK4524101 in combination with niraparib. Both medications are taken by mouth as tablets.

2 Dose observation period

If you are in Part 1, you will enter a dose observation period. During this time, the study doctors will closely monitor you for any side effects or problems with the medication.

The purpose of this period is to determine the appropriate and safe dose of the medication for future participants.

You will be monitored for any dose limiting toxicities, which are serious side effects that may require adjusting the dose or stopping the medication.

3 Ongoing treatment and monitoring

After the initial observation period, you will continue taking your assigned medication.

Throughout the study, the study doctors will monitor your health and any side effects you experience.

Your dose may be adjusted, interrupted, or stopped depending on how you respond to the treatment and any side effects you develop.

Blood samples will be taken at scheduled times to measure the levels of the medication in your body. This helps the study doctors understand how your body processes the medication.

4 Assessment of treatment response

If you are in Part 2, the study doctors will assess whether your cancer responds to the treatment combination.

This will involve regular examinations and tests to determine if the tumors have shrunk, stayed the same, or grown.

The study doctors will also measure how long you remain without cancer progression, known as progression-free survival.

If your cancer responds to treatment, the study doctors will measure how long that response lasts, referred to as duration of response.

5 Food effect assessment

If you are assigned to the food effect cohort in Part 1, you will take the medication under different conditions to see if food affects how your body absorbs the medication.

This may involve taking the medication with food on some days and without food on other days.

Blood samples will be collected to compare the medication levels in your body under these different conditions.

6 Continued participation

You will continue in the study as long as the treatment is helping you and you are not experiencing unacceptable side effects.

Regular visits will be scheduled for examinations, blood tests, and assessments of your overall health and cancer status.

The study is expected to continue until June 2027, although your individual participation may be shorter or longer depending on your response to treatment.

Who Can Join the Study?

You must be 18 years of age or older
Your ECOG performance status must be 0 to 2, which is a scale that measures how well you can perform daily activities and care for yourself, where 0 means you are fully active and 2 means you are able to care for yourself but cannot work
Your doctor expects you to live at least 3 months or longer
For Part 1 of the study: You must have advanced or metastatic solid tumor, which means cancer that has spread beyond where it started or cannot be removed by surgery, and you have already tried all standard treatment options available to you
For Part 2 of the study: You must have metastatic breast cancer, which means breast cancer that has spread to other parts of your body, with a germinal BRCA mutation, which is an inherited change in a gene called BRCA that increases cancer risk, and your cancer must be HER2-negative or HER2-low, which refers to low or absent levels of a protein called HER2 on cancer cells, and you must have completed no more than 3 previous treatment plans for your cancer

Who Cannot Join the Study?

The specific exclusion criteria (reasons why you cannot join this study) have not been provided in the available study information.
Generally, clinical trials exclude patients based on certain health conditions, previous treatments, or other factors that could affect the safety of the study or the results.
If you are interested in this study, you would need to discuss with the study team to learn about all the specific reasons that might prevent you from participating.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name	City	Country
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale	Naples	Italy
Hospital Universitario 12 De Octubre	Madrid	Spain
Hospital San Pedro De Alcantara	Caceres	Spain
Pelican Impex S.R.L.	Oradea	Romania
Centrul De Oncologie SF Nectarie S.R.L.	Craiova	Romania
Odense University Hospital	Odense	Denmark
Tartu University Hospital	Tartu	Estonia
Fakultni Nemocnice Hradec Kralove	Novy Hradec Kralove	Czechia
Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca	Cluj Napoca	Romania
University Hospital Olomouc	Olomouc	Czechia
Radiology Therapeutic Center S.R.L.	Otopeni	Romania
Spitalul De Oncologie Monza S.R.L.	Bucharest	Romania
Fakultni Thomayerova nemocnice	Prague	Czechia
Cjaidtvlr Uuxadtopqmgtef Sihpfgsxu	Woluwe-Saint-Lambert	Belgium
Sth Sbdichh Hgvyaavu Gydkgqz Ahbjogncunh ahr Ozwndceqhwy Hornsvyj oe Ajdqbr	Athens	Greece
Hlzoui Hbuknllh	Herlev	Denmark
Agxuuz Msgbsdl Croudz Stnm	Thessaloniki	Greece
Alvgpui Hhxrsrxr	Athens	Greece

Trial status

Country	Status	Recruitment Start
Belgium	Not recruiting	31.10.2025
Czechia	Not recruiting	31.10.2025
Denmark	Not recruiting	31.10.2025
Estonia	Not recruiting	31.10.2025
Greece	Not recruiting	31.10.2025
Italy	Not recruiting	31.10.2025
Romania	Not recruiting	31.10.2025
Spain	Not recruiting	31.10.2025

Trial locations

Investigated drugs:

GSK4524101 is an oral medication being tested in this study. It works by blocking an enzyme called DNA Polymerase Theta, which helps cancer cells repair their damaged DNA. By stopping this repair process, the medication may help kill cancer cells or slow their growth.

Niraparib is an oral medication that blocks an enzyme called PARP, which also helps cancer cells repair their DNA. When this repair process is blocked, cancer cells may die or stop growing. This medication is being tested in combination with GSK4524101 to see if the two medications work better together than alone.

Investigated diseases:

Neoplasm

Neoplasms – Neoplasms are abnormal growths of tissue that occur when cells divide and grow more than they should or do not die when they should. These growths can develop in any part of the body and may form solid masses called tumors or affect blood-forming tissues. Neoplasms can be benign, meaning they do not spread to other parts of the body, or malignant, meaning they can invade nearby tissues and spread to distant organs through the bloodstream or lymphatic system. The progression of neoplasms varies depending on their type and location, with some growing slowly over many years and others developing rapidly. Advanced neoplasms have grown significantly at their original site, while metastatic neoplasms have spread from their original location to other parts of the body. The behavior and growth pattern of neoplasms depend on various factors including the type of cells involved and genetic changes within those cells.

Breast Cancer – Breast cancer is a disease in which cells in the breast tissue grow abnormally and form a mass or lump. This condition most commonly begins in the milk ducts or the glands that produce milk. The cancer cells can remain confined to the breast tissue or spread to nearby lymph nodes and other parts of the body through the bloodstream. Metastatic breast cancer means the disease has spread beyond the breast and nearby lymph nodes to other organs such as bones, lungs, liver, or brain. HER2-negative breast cancer refers to tumors that do not have excessive amounts of a protein called human epidermal growth factor receptor 2, while HER2-low breast cancer has small amounts of this protein. Some breast cancers are associated with inherited genetic mutations in genes such as BRCA, which affect the body’s ability to repair damaged DNA in cells.

Trial ID:

2024-520197-36-00

Protocol code:

219590

NCT ID:

NCT06077877

Trial Phase:

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

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A Study of GSK4524101 and Niraparib for Adults with Advanced Solid Tumors or Metastatic Breast Cancer with BRCA Gene Changes

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?