NeoplasmsPhase 1/2NCT06077877
A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Anticancer Activity of GSK4524101 Alone or With Niraparib in Participants With Solid Tumors
A Phase 1/2 study testing GSK4524101 and Niraparib in people with Neoplasms, run by GlaxoSmithKline at 11 sites in 3 countries.
Trial summary
The primary purpose of this study is to determine the maximum tolerated dose of GSK4524101 monotherapy (MTD) and GSK4524101 in combination with niraparib (MTDc). The study consists of two parts - Part 1 (Dose Escalation) and Part 2 (Dose Expansion). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- GSK4524101 and Niraparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 24 Oct 2023to 30 Jun 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- More than or equal to (≥)18 years of age
- Eastern cooperative oncology group (ECOG) class 0-2
- Life expectancy of a minimum of 3 month
- Participant has histologically diagnosed advanced or metastatic solid tumor and has exhausted all standard of care treatment options (Part 1).
- Participant has metastatic, gBRCAmut, HER2-negative or HER2-low breast cancer who has completed at most 3 or more prior lines of therapy (Part 2).
Who cannot join
- Participant has not recovered (i.e., to Grade less than or equal to [≤1] or to baseline) from prior chemotherapy-induced AEs.
- Participant is currently participating in a treatment study or has participated in a study of any investigational agent within 4 weeks of the first dose of treatment.
- Participant has symptomatic uncontrolled brain or leptomeningeal metastases.
- Participant has a known additional malignancy that progressed or required active treatment within the last 2 years
- Participant has a known history of Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML).
- Participant has uncontrolled hypertension with sustained systolic blood pressure (BP) >140 millimetres of mercury (mmHg) or diastolic BP >90 mmHg.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States6 sites
GSK Investigational Site
Dallas, Texas, 75230
GSK Investigational Site
Fairfax, Virginia, 22031
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
San Francisco, California, 94158
GSK Investigational Site
St Louis, Missouri, 63110
Canada3 sites
GSK Investigational Site
Edmonton, Alberta, T6G 1Z2
GSK Investigational Site
Montreal, Quebec, H4A 3J1
GSK Investigational Site
Toronto, Ontario, M5G 2M9
Panama2 sites
GSK Investigational Site
Panama City
GSK Investigational Site
Punta Pacifica Panama City Panama
About this study
Official title: A Phase 1/2 First-Time-in-Human, Open-label, Multicenter, Dose Escalation and Expansion Study of the Oral DNA Polymerase Theta Inhibitor (POLQi) GSK4524101 and the PARP Inhibitor (PARPi) Niraparib in Adult Participants With Solid Tumors
The primary purpose of this study is to determine the maximum tolerated dose of GSK4524101 monotherapy (MTD) and GSK4524101 in combination with niraparib (MTDc). The study consists of two parts - Part 1 (Dose Escalation) and Part 2 (Dose Expansion).
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK4524101Drug
GSK452101 will be administered.
NiraparibDrug
Niraparib will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 - GSK4524101 Monotherapy | Experimental | Not described Receives: Drug: GSK4524101 |
| Part 1 - GSK4524101 plus Niraparib | Experimental | Not described Receives: Drug: GSK4524101; Drug: Niraparib |
| Part 1 - GSK4524101 Food Effect Cohort | Experimental | Not described Receives: Drug: GSK4524101 |
| Part 2 - GSK4524101 plus Niraparib | Experimental | Not described Receives: Drug: GSK4524101; Drug: Niraparib |
| Part 2 - Niraparib | Active comparator | Not described Receives: Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1 - Proportion of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period
Measured: Up to 28 days
Part 1 - Proportion of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) based on Severity during DLT Observation Period
Measured: Up to 28 days
Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period
Measured: Up to 28 days
Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period
Measured: Up to 28 days
Part 1 -Percentage of Participants who require dosage interruptions, dose reductions, and drug discontinuations due to adverse reactions during DLT Observation Period
Measured: Up to 28 days
Part 2 - Confirmed Objective Response Rate (ORR)
ORR is the percentage of participants with an Investigator-assessed confirmed complete response and confirmed partial response to treatment, as assessed by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1
Measured: Up to approximately 52 weeks
Secondary outcomes (14)
Part 1 - Area Under Curve (AUC) of GSK4364973 (Metabolite of GSK4524101)
Measured: Up to 21 weeks
Part 1 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)
Measured: Up to 21 weeks
Part 1 - Time to Maximum Concentration of GSK4364973 (Metabolite of GSK4524101)
Measured: Up to 21 weeks
Part 1 - Half-life of GSK4364973 (Metabolite of GSK4524101) (Days)
Measured: Up to 21 weeks
Part 1 -Plasma Concentration of Niraparib
Measured: Up to 21 weeks
Part 1 - Number of Participants with TEAEs and SAEs based on Severity beyond DLT Observation Period
Measured: Up to approximately 24 weeks
Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period
Measured: Up to approximately 24 weeks
Part 2 - Number of Participants with TEAEs and SAEs based on Severity
Measured: Up to approximately 52 weeks
Part 2 - Duration of Treatment Emergent AEs and SAEs (Days)
Measured: Up to approximately 52 weeks
Part 2 - Progression-free Survival (PFS)
PFS is time from randomization to progressive disease or death from any cause, whichever is earlier, as assessed via RECIST v1.1 by Investigator assessment
Measured: Up to approximately 52 weeks
Part 2 - Duration of Response (DOR)
DOR is defined as time from first documented PR or better to disease progression (as assessed by RECIST v1.1 by investigator assessment) or death whichever is earlier for participants who have achieved a CR or PR
Measured: Up to approximately 52 weeks
Part 2 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)
Measured: Up to 21 weeks
Part 2 - Minimum Concentration (Cmin) of GSK4364973 (Metabolite of GSK4524101)
Measured: Up to 21 weeks
Part 2 -Plasma Concentration of Niraparib
Measured: Up to 21 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2023
- Study start24 Oct 2023
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06077877
- Sponsor's protocol ID
- 219590
- Status last verified
- Apr 2026
- First submitted
- 5 Oct 2023
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 First-Time-in-Human, Open-label, Multicenter, Dose Escalation and Expansion Study of the Oral DNA Polymerase Theta Inhibitor (POLQi) GSK4524101 and the PARP Inhibitor (PARPi) Niraparib in Adult Participants With Solid Tumors
- ClinicalTrials.gov ID
- NCT06077877
- Acronym / sponsor ID
- 219590
- Conditions
- Neoplasms
- Keywords
- POLQi, Niraparib, GSK4524101
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 42 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2023 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 11 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to determine the maximum tolerated dose of GSK4524101 monotherapy (MTD) and GSK4524101 in combination with niraparib (MTDc). The study consists of two parts - Part 1 (Dose Escalation) and Part 2 (Dose Expansion).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1 - GSK4524101 Monotherapy | Experimental | Drug: GSK4524101 |
| Part 1 - GSK4524101 plus Niraparib | Experimental | Drug: GSK4524101, Drug: Niraparib |
| Part 1 - GSK4524101 Food Effect Cohort | Experimental | Drug: GSK4524101 |
| Part 2 - GSK4524101 plus Niraparib | Experimental | Drug: GSK4524101, Drug: Niraparib |
| Part 2 - Niraparib | Active comparator | Drug: Niraparib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- More than or equal to (≥)18 years of age
- Eastern cooperative oncology group (ECOG) class 0-2
- Life expectancy of a minimum of 3 month
- Participant has histologically diagnosed advanced or metastatic solid tumor and has exhausted all standard of care treatment options (Part 1).
- Participant has metastatic, gBRCAmut, HER2-negative or HER2-low breast cancer who has completed at most 3 or more prior lines of therapy (Part 2).
Key exclusion criteria (6 listed)
- Participant has not recovered (i.e., to Grade less than or equal to [≤1] or to baseline) from prior chemotherapy-induced AEs.
- Participant is currently participating in a treatment study or has participated in a study of any investigational agent within 4 weeks of the first dose of treatment.
- Participant has symptomatic uncontrolled brain or leptomeningeal metastases.
- Participant has a known additional malignancy that progressed or required active treatment within the last 2 years
- Participant has a known history of Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK4524101GSK452101 will be administered. | Drug | Part 1 - GSK4524101 Food Effect Cohort, Part 1 - GSK4524101 Monotherapy, Part 1 - GSK4524101 plus Niraparib, Part 2 - GSK4524101 plus Niraparib |
| NiraparibNiraparib will be administered. | Drug | Part 1 - GSK4524101 plus Niraparib, Part 2 - GSK4524101 plus Niraparib, Part 2 - Niraparib |
Primary outcome
Part 1 - Proportion of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period
Time frame: Up to 28 days
Part 1 - Proportion of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) based on Severity during DLT Observation Period
Time frame: Up to 28 days
Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period
Time frame: Up to 28 days
Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period
Time frame: Up to 28 days
Part 1 -Percentage of Participants who require dosage interruptions, dose reductions, and drug discontinuations due to adverse reactions during DLT Observation Period
Time frame: Up to 28 days
Part 2 - Confirmed Objective Response Rate (ORR)
Time frame: Up to approximately 52 weeks
ORR is the percentage of participants with an Investigator-assessed confirmed complete response and confirmed partial response to treatment, as assessed by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1
14 secondary outcomes
Part 1 - Area Under Curve (AUC) of GSK4364973 (Metabolite of GSK4524101)
Time frame: Up to 21 weeks
Part 1 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)
Time frame: Up to 21 weeks
Part 1 - Time to Maximum Concentration of GSK4364973 (Metabolite of GSK4524101)
Time frame: Up to 21 weeks
Part 1 - Half-life of GSK4364973 (Metabolite of GSK4524101) (Days)
Time frame: Up to 21 weeks
Part 1 -Plasma Concentration of Niraparib
Time frame: Up to 21 weeks
Part 1 - Number of Participants with TEAEs and SAEs based on Severity beyond DLT Observation Period
Time frame: Up to approximately 24 weeks
Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period
Time frame: Up to approximately 24 weeks
Part 2 - Number of Participants with TEAEs and SAEs based on Severity
Time frame: Up to approximately 52 weeks
Part 2 - Duration of Treatment Emergent AEs and SAEs (Days)
Time frame: Up to approximately 52 weeks
Part 2 - Progression-free Survival (PFS)
Time frame: Up to approximately 52 weeks
Part 2 - Duration of Response (DOR)
Time frame: Up to approximately 52 weeks
Part 2 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)
Time frame: Up to 21 weeks
Part 2 - Minimum Concentration (Cmin) of GSK4364973 (Metabolite of GSK4524101)
Time frame: Up to 21 weeks
Part 2 -Plasma Concentration of Niraparib
Time frame: Up to 21 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GSK4524101 and Niraparib in people with Neoplasms, run by GlaxoSmithKline at 11 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada, Panama. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1 - Proportion of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period (time frame: Up to 28 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.