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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 42
- 试验地点
- 11
- 主要终点
- Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label non-blinded study
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
Part 1 - GSK4524101 Monotherapy
干预措施: GSK4524101 (Drug)
Part 1 - GSK4524101 plus Niraparib
干预措施: Niraparib (Drug)
Part 2 - GSK4524101 plus Niraparib
干预措施: Niraparib (Drug)
Part 2 - GSK4524101 plus Niraparib
干预措施: GSK4524101 (Drug)
Part 1 - GSK4524101 Food Effect Cohort
干预措施: GSK4524101 (Drug)
Part 1 - GSK4524101 plus Niraparib
干预措施: GSK4524101 (Drug)
Part 2 - Niraparib
干预措施: Niraparib (Drug)
结局指标
主要结局
Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period
时间窗: Up to 28 days
Part 1 - Proportion of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period
时间窗: 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
时间窗: Up to 28 days
Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period
时间窗: 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
时间窗: Up to 28 days
Part 2 - Confirmed Objective Response Rate (ORR)
时间窗: 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
次要结局
- 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)
- Part 1 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)(Up to 21 weeks)
- Part 2 -Plasma Concentration of Niraparib(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)
- 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)