A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Anticancer Activity of GSK4524101 Alone or With Niraparib in Participants With Solid Tumors
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 - GSK4524101 Monotherapy
|
Drug: GSK4524101
GSK452101 will be administered.
|
| Experimental: Part 1 - GSK4524101 plus Niraparib
|
Drug: GSK4524101
GSK452101 will be administered.
Drug: Niraparib
Niraparib will be administered.
|
| Experimental: Part 1 - GSK4524101 Food Effect Cohort
|
Drug: GSK4524101
GSK452101 will be administered.
|
| Experimental: Part 2 - GSK4524101 plus Niraparib
|
Drug: GSK4524101
GSK452101 will be administered.
Drug: Niraparib
Niraparib will be administered.
|
| Active Comparator: Part 2 - Niraparib
|
Drug: Niraparib
Niraparib will be administered.
|
Outcome Measures
Primary Outcome Measures
- Part 1 - Number of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period [Up to 28 days]
- Part 1 - Number 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 Outcome Measures
- 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]
Eligibility Criteria
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.
Exclusion Criteria:
-
Participant has not recovered (i.e., to Grade less than or equal to [≤1] or to baseline) from prior chemotherapy-induced AEs.
-
First-line locally advanced or metastatic breast cancer with no prior chemotherapy
-
Inflammatory breast cancer
-
Prior treatment with a Poly (ADP [Adenosine Diphosphate]-ribose) polymerase inhibitors (PARPi)
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | San Francisco | California | United States | 94158 |
| 2 | GSK Investigational Site | Saint Louis | Missouri | United States | 63110 |
| 3 | GSK Investigational Site | Dallas | Texas | United States | 75230 |
| 4 | GSK Investigational Site | Houston | Texas | United States | 77030 |
| 5 | GSK Investigational Site | San Antonio | Texas | United States | 78229 |
| 6 | GSK Investigational Site | Fairfax | Virginia | United States | 22031 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 219590