GSK4524101 + Niraparib for Cancer

Recruiting at 11 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GlaxoSmithKline

Disqualifiers: Uncontrolled hypertension, Brain metastases, MDS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

135 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment called GSK4524101, both alone and in combination with another drug, niraparib. The goal is to determine the highest dose patients can tolerate without serious side effects. It targets individuals with advanced cancers, particularly those with HER2-negative breast cancer who have tried multiple treatments unsuccessfully. Participants should have a solid tumor that has not responded to standard treatments. This trial is for individuals who have exhausted their current cancer treatment options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GSK4524101, a new drug under study, is being tested for safety and tolerability. Researchers aim to determine the maximum dosage that can be administered without causing serious side effects. In these studies, GSK4524101 is tested both alone and in combination with another drug, niraparib.

When tested alone, niraparib was generally well-tolerated by patients with advanced solid tumors, meaning most could take it without major issues. A study with Japanese patients reported only one significant side effect.

As GSK4524101 is in the early testing stages, researchers continue to assess its safety. This phase focuses on identifying the appropriate dose and monitoring for side effects. While some side effects may occur, these studies ensure the treatment's safety for future use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GSK4524101 and its combination with Niraparib because they offer a novel approach to treating cancer. Unlike standard treatments that often target cancer cells broadly, GSK4524101 is designed to work by inhibiting specific pathways that cancer cells depend on for survival. This precision approach could potentially lead to fewer side effects and more effective suppression of tumor growth. Additionally, the combination with Niraparib, a PARP inhibitor, may enhance the treatment's effectiveness by preventing cancer cells from repairing themselves, leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that the combination of GSK4524101 and niraparib, tested in this trial, may help treat certain cancers. Niraparib, one of the treatments in this trial, is a drug known to help ovarian cancer patients live longer without disease progression. In early studies, about 78% of patients who received GSK4524101, another treatment option in this trial, experienced tumor shrinkage. Additionally, this treatment's effects appeared to last, as several patients continued without significant disease progression. These results suggest that this combination might be effective for some solid tumors. ^{1 3 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

Adults (18+) with advanced or metastatic solid tumors who have no remaining standard treatment options can join. They should be fairly active and mobile (ECOG 0-2) and expected to live at least 3 more months. People are excluded if they haven't recovered from previous chemo side effects, have certain types of breast cancer, used PARP inhibitors, or have specific blood cancers, uncontrolled high blood pressure, or untreated brain metastases.

Inclusion Criteria

I have an advanced cancer and no standard treatments are left.

I am able to care for myself and perform daily activities.

You are expected to live for at least 3 more months.

Exclusion Criteria

I have inflammatory breast cancer.

I have a history of Myelodysplastic syndrome or Acute myeloid leukemia.

My breast cancer is advanced or has spread, and I haven't had chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive GSK4524101 monotherapy or GSK4524101 in combination with niraparib to determine the maximum tolerated dose

Up to approximately 52 weeks

Dose Expansion

Participants receive GSK4524101 in combination with niraparib to further evaluate safety and efficacy

Up to approximately 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GSK4524101
• Niraparib

Trial Overview The trial is testing GSK4524101 alone and combined with Niraparib to find the highest dose patients can tolerate without severe side effects. It's in two stages: first finding the right doses (Dose Escalation), then giving those doses to more people to see how well they work (Dose Expansion).

How Is the Trial Designed?

Group I: Part 2 - GSK4524101 plus Niraparib Experimental Treatment 2 Interventions

Group II: Part 1 - GSK4524101 plus Niraparib Experimental Treatment 2 Interventions

Group III: Part 1 - GSK4524101 Monotherapy Experimental Treatment 1 Intervention

Group IV: Part 1 - GSK4524101 Food Effect Cohort Experimental Treatment 1 Intervention

Group V: Part 2 - Niraparib Active Control 1 Intervention

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

Niraparib is an FDA and EMA-approved oral PARP inhibitor for maintenance treatment in women with recurrent ovarian cancer who have responded to platinum-based chemotherapy, showing efficacy in both BRCA mutated and wild-type cancers.

While niraparib is effective, it can cause significant hematologic toxicities, such as thrombocytopenia and anemia, necessitating dose adjustments for certain patients to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. Moore, KN., Mirza, MR., Matulonis, UA.[2019]

Niraparib is an effective PARP inhibitor for maintenance treatment in ovarian cancer patients, particularly those with BRCA mutations, following platinum-based chemotherapy.

This report highlights a previously unreported case of severe pulmonary embolism in a patient treated with niraparib, emphasizing the need for awareness of this potential serious side effect despite its generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Niraparib-Related Pulmonary Embolism During the Treatment of BRCA Mutant Advanced Ovarian Cancer. Wei, Q., Chen, DS., Liu, YH.[2022]

Niraparib, administered at doses of 200 mg and 300 mg daily, was found to be tolerable in Japanese patients with advanced solid tumors, with only one case of dose-limiting toxicity observed.

The study demonstrated a favorable pharmacokinetic profile for niraparib, with dose-proportional increases in drug levels and some patients showing a partial response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety, tolerability and pharmacokinetics of niraparib in Japanese patients with solid tumours: results of a phase I dose-escalation study. Yonemori, K., Shimizu, T., Kondo, S., et al.[2021]

Niraparib, a PARP inhibitor for recurrent ovarian cancer, showed no significant changes in its pharmacokinetics when taken with a high-fat meal compared to fasting, indicating it can be safely taken with or without food.

The study demonstrated that niraparib was well-tolerated and had similar adverse events regardless of the meal condition, confirming its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer. Moore, K., Zhang, ZY., Agarwal, S., et al.[2019]

In the ENGOT-OV16/NOVA trial, patients aged 70 and older with recurrent ovarian cancer who received niraparib showed significant progression-free survival (PFS) benefits, with non-gBRCAmut patients achieving a median PFS of 11.3 months compared to 3.8 months for those on placebo.

The safety profile of niraparib in older patients was similar to that in younger patients, with common adverse events being hematologic issues like thrombocytopenia and anemia, suggesting that niraparib is a viable treatment option for older patients with recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial. Fabbro, M., Moore, KN., Dørum, A., et al.[2019]

In a phase III trial involving patients with advanced breast cancer and germline BRCA1/2 mutations, niraparib showed a median progression-free survival (PFS) of 4.1 months compared to 3.1 months for physician's choice chemotherapy, although the difference was not statistically significant (P = 0.86).

Despite the trial being halted due to issues with data assessment, niraparib demonstrated a 35% objective response rate, indicating its potential effectiveness in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study. Turner, NC., Balmaña, J., Poncet, C., et al.[2023]

In a Phase 2 study involving 20 Japanese women with heavily pretreated ovarian cancer, niraparib demonstrated an objective response rate of 35%, indicating that it can effectively reduce tumor size in some patients.

The treatment was generally well-tolerated, with a high disease control rate of 90%, although common side effects included anemia and nausea, and 70% of patients experienced dose reductions or interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. Okamoto, A., Kondo, E., Nakamura, T., et al.[2021]

Niraparib, a PARP inhibitor, has been shown to be safe for long-term use in patients with recurrent ovarian cancer, with a significant reduction in treatment-emergent adverse events (TEAEs) over time, particularly in the first month of treatment.

The study highlighted the importance of dose adjustments, as the incidence of severe side effects like thrombocytopenia decreased significantly after the initial month, indicating that careful management can enhance the safety of niraparib therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Mirza, MR., Benigno, B., Dørum, A., et al.[2021]

In a study of 94 patients with non-gBRCA1/2 mutated recurrent ovarian cancer, niraparib maintenance treatment demonstrated effectiveness similar to phase III trials, with a median time to first subsequent treatment of 10.7 months.

Individualized dosing based on patient weight and platelet counts led to fewer dose reductions and interruptions, highlighting the importance of personalized treatment to enhance safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer. Vilming, B., Fallås Dahl, J., Bentzen, AG., et al.[2023]

In a phase 3 trial involving 733 patients with newly diagnosed advanced ovarian cancer, niraparib significantly improved progression-free survival compared to placebo, with a median of 21.9 months versus 10.4 months for patients with homologous-recombination deficiency.

Niraparib also demonstrated a notable overall survival rate of 84% at 24 months, with manageable side effects, including anemia and thrombocytopenia, but no treatment-related deaths, indicating its safety and efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. González-Martín, A., Pothuri, B., Vergote, I., et al.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS3174

A phase 1/2 dose escalation study of the oral DNA ... This first-in-human study investigates treatment with GSK4524101, an investigational POLQi, and niraparib, a PARPi, in patients with solid tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06077877

NCT06077877 | A Study to Investigate the Safety, ... The primary purpose of this study is to determine the maximum tolerated dose of GSK4524101 monotherapy (MTD) and GSK4524101 in combination with niraparib ...

3. withpower.com withpower.com/trial/phase-2-neoplasms-10-2023-0ceb0

GSK4524101 + Niraparib for Cancer Research shows that Niraparib, one of the drugs in the treatment, has been effective in increasing the time patients with ovarian cancer live without the ...

4. synapse.patsnap.com synapse.patsnap.com/drug/88afe7b8116249659182e57e1b8571ff

GSK-4524101 - Drug Targets, Indications, Patents Reported positive interim data from 18 evaluable urothelial cancer and NSCLC patients. ... outcomes for urothelial cancer patients. IDE161 Program in Tumors with ...

5. ir.ideayabio.com ir.ideayabio.com/2024-11-04-IDEAYA-Biosciences,-Inc-Reports-Third-Quarter-2024-Financial-Results-and-Provides-Business-Update

/C O R R E C T I O N -- IDEAYA Biosciences, Inc./ - Nov 4, ... Following a successful Type C meeting with the U.S. Food and Drug Administration (FDA), IDEAYA is finalizing the Phase 3 registrational trial ...

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/dna-polymerase-theta-inhibitor-gsk4524101?pn=1

Clinical Trials Using DNA Polymerase Theta Inhibitor ... NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying dna polymerase theta inhibitor gsk4524101.

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/437216

A Study to Investigate the Safety, Tolerability ... The primary purpose of this study is to determine the maximum tolerated dose of GSK4524101 monotherapy (MTD) and GSK4524101 in combination with niraparib (MTDc ...

8. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2025.43.16_suppl.TPS3174

A phase 1/2 dose escalation study of the oral DNA ... To evaluate the clinical potential of this combination, this first- in-human study investigates treatment with GSK4524101, an investigational POLQi, and.