A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Anticancer Activity of GSK4524101 Alone or With Niraparib in Participants With Solid Tumors

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Niraparib; Drug: GSK4524101

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • GSK Investigational Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • GSK Investigational Site
• Panama
  • Panama City, Panama
    • GSK Investigational Site
  • Punta Pacifica Panama City Panama, Panama
    • GSK Investigational Site
• United States
  • California
    • San Francisco, California, United States, 94158
      • GSK Investigational Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • GSK Investigational Site
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - GSK4524101 Monotherapy	Drug: GSK4524101; GSK452101 will be administered.
Experimental: Part 1 - GSK4524101 plus Niraparib	Drug: Niraparib; Niraparib will be administered.; Drug: GSK4524101; GSK452101 will be administered.
Experimental: Part 1 - GSK4524101 Food Effect Cohort	Drug: GSK4524101; GSK452101 will be administered.
Experimental: Part 2 - GSK4524101 plus Niraparib	Drug: Niraparib; Niraparib will be administered.; Drug: GSK4524101; GSK452101 will be administered.
Active Comparator: Part 2 - Niraparib	Drug: Niraparib; Niraparib will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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	Up to approximately 52 weeks
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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	Up to approximately 52 weeks
Part 2 - Duration of Response (DOR)	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	Up to approximately 52 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
Part 2 -Plasma Concentration of Niraparib		Up to 21 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: October 5, 2023
• First Posted (Actual): October 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Niraparib; POLQi; GSK4524101
• Additional Relevant MeSH Terms: Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; niraparib
• Other Study ID Numbers: 219590

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No