GSK4524101 + Niraparib for Cancer

Recruiting at 9 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: GlaxoSmithKline

Disqualifiers: Uncontrolled hypertension, Brain metastases, MDS, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called GSK4524101 alone and with another drug called niraparib. It aims to find the highest safe dose and understand its effects, likely targeting cancer patients who need new treatment options. Niraparib is a drug taken by mouth that is used to maintain treatment in ovarian cancer.

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.

What data supports the effectiveness of the drug 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 disease getting worse, especially after chemotherapy. It has also shown promise in treating advanced breast cancer with specific genetic mutations. ^{1 2 3 4 5}

What safety information is available for the cancer treatment GSK4524101 + Niraparib?

Niraparib, a part of the treatment, has been studied for safety in patients with ovarian cancer. Common side effects include blood-related issues like low platelet counts, anemia, and low white blood cell counts, as well as fatigue and high blood pressure. Rare but serious risks include blood clots and a small chance of developing certain blood cancers. ^{1 6 7 8 9}

What makes the drug GSK4524101 + Niraparib unique for cancer treatment?

The combination of GSK4524101 and Niraparib is unique because it involves Niraparib, an oral drug that inhibits PARP enzymes, which are involved in DNA repair, making it effective for certain cancers regardless of BRCA mutation status. This combination may offer a novel approach by potentially enhancing the effects of Niraparib with GSK4524101, although specific details about GSK4524101's role are not provided in the available research. ^{1 2 6 7 10}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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 18 years old or older.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• GSK4524101 (Other)
• Niraparib (Other)

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).

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

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, 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]

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]

References

1. United States 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. [2023]

2. United States 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. [2019]

3. Korea (South) 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. [2019]

6. Germany 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. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Niraparib-Related Pulmonary Embolism During the Treatment of BRCA Mutant Advanced Ovarian Cancer. [2022]

9. United States 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. [2021]

10. England 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. [2021]