Neoplasms
Conditions
Keywords
POLQi, Niraparib, GSK4524101
Brief 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).
Interventions
DRUGGSK4524101
GSK452101 will be administered.
DRUGNiraparib
Niraparib will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label non-blinded study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 - Proportion of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period | 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 | Up to 28 days | — |
| Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period | Up to 28 days | — |
| Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period | 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 | Up to 28 days | — |
| Part 2 - Confirmed Objective Response Rate (ORR) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 - Area Under Curve (AUC) of GSK4364973 (Metabolite of GSK4524101) | Up to 21 weeks | — |
| Part 1 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101) | Up to 21 weeks | — |
| Part 1 - Time to Maximum Concentration of GSK4364973 (Metabolite of GSK4524101) | Up to 21 weeks | — |
| Part 1 - Half-life of GSK4364973 (Metabolite of GSK4524101) (Days) | Up to 21 weeks | — |
| Part 1 -Plasma Concentration of Niraparib | Up to 21 weeks | — |
| Part 1 - Number of Participants with TEAEs and SAEs based on Severity beyond DLT Observation Period | Up to approximately 24 weeks | — |
| Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period | Up to approximately 24 weeks | — |
| Part 2 - Number of Participants with TEAEs and SAEs based on Severity | Up to approximately 52 weeks | — |
| Part 2 - Duration of Treatment Emergent AEs and SAEs (Days) | Up to approximately 52 weeks | — |
| Part 2 - Progression-free Survival (PFS) | Up to approximately 52 weeks | 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 |
| Part 2 - Duration of Response (DOR) | Up to approximately 52 weeks | 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 |
| Part 2 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101) | Up to 21 weeks | — |
| Part 2 - Minimum Concentration (Cmin) of GSK4364973 (Metabolite of GSK4524101) | Up to 21 weeks | — |
| Part 2 -Plasma Concentration of Niraparib | Up to 21 weeks | — |
Countries
Canada, Panama, United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Outcome results
None listed