A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Anticancer Activity of GSK4524101 Alone or With Niraparib in Participants With Solid Tumors
- Registration Number
- NCT06077877
- Lead Sponsor
- GlaxoSmithKline
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 135
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 - GSK4524101 Food Effect Cohort GSK4524101 - Part 2 - GSK4524101 plus Niraparib GSK4524101 - Part 1 - GSK4524101 Monotherapy GSK4524101 - Part 1 - GSK4524101 plus Niraparib GSK4524101 - Part 1 - GSK4524101 plus Niraparib Niraparib - Part 2 - GSK4524101 plus Niraparib Niraparib - Part 2 - Niraparib Niraparib -
- Primary Outcome Measures
Name Time Method 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 - 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 -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
Name Time Method Part 2 -Plasma Concentration of Niraparib Up to 21 weeks Part 1 - Half-life of GSK4364973 (Metabolite of GSK4524101) (Days) Up to 21 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 1 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101) Up to 21 weeks Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period Up to approximately 24 weeks Part 2 - Duration of Treatment Emergent AEs and SAEs (Days) Up to approximately 52 weeks 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 1 - Time to Maximum Concentration of GSK4364973 (Metabolite of GSK4524101) 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 2 - Number of Participants with TEAEs and SAEs based on Severity Up to approximately 52 weeks Part 1 - Area Under Curve (AUC) of GSK4364973 (Metabolite of GSK4524101) Up to 21 weeks Part 1 -Plasma Concentration of Niraparib Up to 21 weeks 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
Trial Locations
- Locations (1)
GSK Investigational Site
🇨🇦Toronto, Ontario, Canada