What is the mechanism of action of this treatment?

PARP inhibitors, such as Niraparib, block the PARP enzyme involved in DNA repair, leading to cancer cell death, particularly in cells with existing DNA repair deficiencies. This mechanism is vital for tumor patients as it directly targets the cancer cells' survival mechanisms. Investigational therapies like GSK4524101, though not fully detailed, typically aim to disrupt key molecular pathways essential for tumor growth, providing potential new treatment options for resistant or aggressive cancers.

What side effects are associated with this type of intervention?

Common side effects of treatments similar to GSK4524101 and Niraparib include hematologic toxicities such as anemia, thrombocytopenia, and neutropenia. Non-hematologic side effects often observed with Niraparib, a PARP inhibitor, include nausea, fatigue, and anorexia. For investigational drugs like GSK4524101, side effects can vary but may include gastrointestinal disturbances, fatigue, and hematologic abnormalities.

What prior FDA approvals exist?

Niraparib, a PARP inhibitor, has been approved by the FDA for the treatment of various cancers, including ovarian and prostate cancers. Other PARP inhibitors like Olaparib and Rucaparib have also received FDA approval for similar indications, particularly in cancers with BRCA mutations or other homologous recombination repair deficiencies. These drugs work by inhibiting the PARP enzyme, which is crucial for DNA repair in cancer cells, leading to cell death. Additionally, treatments like Pembrolizumab, an immune checkpoint inhibitor, have been approved for various tumors, highlighting the trend towards targeted and personalized cancer therapies.

What other types of research exist?

Promising novel alternatives for tumor patients in 2024 include: 1) Olaparib and Rucaparib, which are other PARP inhibitors showing efficacy in various cancers. 2) Abiraterone combined with Olaparib, which has shown promising results in metastatic castration-resistant prostate cancer. 3) Targeted therapies like Afatinib for NRG1-positive lung cancer and selective RET inhibitors like Selpercatinib for RET-altered thyroid cancers. 4) Immunotherapies and combination therapies, such as chemoimmunotherapy, which are being actively researched and developed.

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GSK4524101 + Niraparib for Cancer

Phase 1 & 2

Recruiting

Research Sponsored by GlaxoSmithKline

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant has histologically diagnosed advanced or metastatic solid tumor and has exhausted all standard of care treatment options.

More than or equal to (≥)18 years of age

Must not have

Inflammatory breast cancer

Participant has a known history of Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 52 weeks

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

Possible side effects include typical reactions related to chemotherapy such as nausea, fatigue, low blood counts leading to increased infection risk or bleeding problems. Specific risks may also involve issues due to drug interactions between GSK4524101 and Niraparib.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 18 years old or older.

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have inflammatory breast cancer.

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

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

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I have uncontrolled brain cancer symptoms.

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I have been treated with PARP inhibitors before.

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My blood pressure is consistently higher than 140/90 mmHg.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 52 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 52 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 52 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 2 - Confirmed Objective Response Rate (ORR)

Secondary study objectives

Part 2 - Duration of Response (DOR)

Part 2 - Progression-free Survival (PFS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Part 2 - GSK4524101 plus NiraparibExperimental Treatment2 Interventions

Group II: Part 1 - GSK4524101 plus NiraparibExperimental Treatment2 Interventions

Group III: Part 1 - GSK4524101 MonotherapyExperimental Treatment1 Intervention

Group IV: Part 1 - GSK4524101 Food Effect CohortExperimental Treatment1 Intervention

Group V: Part 2 - NiraparibActive Control1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Niraparib

2018

Completed Phase 4

~2400

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

PARP inhibitors, such as Niraparib, block the PARP enzyme involved in DNA repair, leading to cancer cell death, particularly in cells with existing DNA repair deficiencies. This mechanism is vital for tumor patients as it directly targets the cancer cells' survival mechanisms. Investigational therapies like GSK4524101, though not fully detailed, typically aim to disrupt key molecular pathways essential for tumor growth, providing potential new treatment options for resistant or aggressive cancers.

Promising novel therapies for the treatment of endometrial cancer.