Last updated: 06/03/2025 17:30:25
A study to investigate the safety, tolerability, pharmacokinetics (PK), and preliminary anticancer activity of GSK4524101 alone or with niraparib in participants with solid tumors
GSK study ID
219590
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Recruiting
Recruiting
Trial overview
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
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Part 1 - Proportion of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period
Timeframe: 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
Timeframe: Up to 28 days
Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period
Timeframe: Up to 28 days
Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period
Timeframe: 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
Timeframe: Up to 28 days
Part 2 - Confirmed Objective Response Rate (ORR)
Timeframe: Up to approximately 52 weeks
Secondary outcomes:
Part 1 – Area Under Curve (AUC) of GSK4364973 (Metabolite of GSK4524101)
Timeframe: Up to 21 weeks
Part 1 –Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)
Timeframe: Up to 21 weeks
Part 1 – Time to Maximum Concentration of GSK4364973 (Metabolite of GSK4524101)
Timeframe: Up to 21 weeks
Part 1 – Half-life of GSK4364973 (Metabolite of GSK4524101) (Days)
Timeframe: Up to 21 weeks
Part 1 –Plasma Concentration of Niraparib
Timeframe: Up to 21 weeks
Part 1 – Number of Participants with TEAEs and SAEs based on Severity beyond DLT Observation Period
Timeframe: Up to approximately 24 weeks
Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period
Timeframe: Up to approximately 24 weeks
Part 2 – Number of Participants with TEAEs and SAEs based on Severity
Timeframe: Up to approximately 52 weeks
Part 2 - Duration of Treatment Emergent AEs and SAEs (Days)
Timeframe: Up to approximately 52 weeks
Part 2 – Progression-free Survival (PFS)
Timeframe: Up to approximately 52 weeks
Part 2 - Duration of Response (DOR)
Timeframe: Up to approximately 52 weeks
Part 2 –Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)
Timeframe: Up to 21 weeks
Part 2 – Minimum Concentration (Cmin) of GSK4364973 (Metabolite of GSK4524101)
Timeframe: Up to 21 weeks
Part 2 –Plasma Concentration of Niraparib
Timeframe: Up to 21 weeks
Interventions:
Enrollment:
135
Primary completion date:
2027-29-06
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms
Product
GSK4524101
Collaborators
Not applicable
Study date(s)
October 2023 to June 2027
Type
Interventional
Phase
1/2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- More than or equal to (≥)18 years of age
- Eastern cooperative oncology group (ECOG) class 0-2
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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).
Exclusion criteria:
- 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 location(s)
Showing 1 - 6 of 9 Results
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Recruiting
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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