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

NCT06077877 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 219590
• Study Type: interventional
• Target: 42
• Locations: 3 countries
• Sites: 11

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).

Conditions

Neoplasms

Keywords

POLQi; Niraparib; GSK4524101

Outcome Measures

Primary Outcomes (6)

• 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)

  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

Secondary Outcomes (14)

• 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

Study Arms (5)

Part 1 - GSK4524101 Monotherapy

EXPERIMENTAL

Drug: GSK4524101

Part 1 - GSK4524101 plus Niraparib

EXPERIMENTAL

Drug: GSK4524101; Drug: Niraparib

Part 1 - GSK4524101 Food Effect Cohort

EXPERIMENTAL

Drug: GSK4524101

Part 2 - GSK4524101 plus Niraparib

EXPERIMENTAL

Drug: GSK4524101; Drug: Niraparib

Part 2 - Niraparib

ACTIVE COMPARATOR

Drug: Niraparib

Interventions

GSK4524101 DRUG

GSK452101 will be administered.

Part 1 - GSK4524101 Food Effect Cohort; Part 1 - GSK4524101 Monotherapy; Part 1 - GSK4524101 plus Niraparib; Part 2 - GSK4524101 plus Niraparib

Niraparib DRUG

Niraparib will be administered.

Part 1 - GSK4524101 plus Niraparib; Part 2 - GSK4524101 plus Niraparib; Part 2 - Niraparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (11)

GSK Investigational Site

San Francisco, California, 94158, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Fairfax, Virginia, 22031, United States

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

Location

GSK Investigational Site

Panama City, Panama

Location

GSK Investigational Site

Punta Pacifica Panama City Panama, Panama

Location

MeSH Terms

Conditions

Neoplasms

Interventions

niraparib

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label non-blinded study
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: October 11, 2023
• Study Start: October 24, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (6); CA (3); PA (2)