A study to investigate the safety, tolerability, pharmacokinetics (PK), and preliminary anticancer activity of GSK4524101 alone or with niraparib in participants with solid tumors.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 9 Dec 2025

Decision date (initial)

2025-11-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2024-520197-36-00

ClinicalTrials.gov

NCT06077877

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Part 1 (Dose Escalation): To determine the MTD and the MTDc based on the safety, available PK, and available pharmacodynamic profiles observed after oral administration of GSK4524101 monotherapy (MTD) and in combination with niraparib (MTDc). The dose escalation will be conducted in adult participants with advanced or metastatic solid tumors who have exhausted all standard of care treatment options. The study will preferentially enroll participants who may potentially benefit based upon mechanism of action of POLQi or PARPi. Part 1 will also include a food effect cohort.
Part 2 (Dose Expansion): To investigate the preliminary clinical activity of GSK4524101 in combination with niraparib at a dose lower, at, or near (but not above) the MTDc tested in Part 1 and to provide proof-of-concept for the GSK4524101 and niraparib combination. The dose expansion will enroll adult participants with metastatic, gBRCAmut, HER2-negative or HER2-low breast cancer who have completed at most 3 lines of prior therapy and are PARPi-naïve.

Secondary objectives 6

1. Part 1 – Characterize PK or exposure of GSK4364973 after administration of GSK4524101 as monotherapy and in combination with niraparib
2. Part 1 – Characterize PK or exposure of niraparib when administered in combination with GSK4524101
3. Part 1 – Assess the long-term safety and tolerability of GSK4524101 and niraparib combination
4. Part 2 – Further evaluate the safety of GSK4524101 in combination with niraparib administered in the dose expansion regimen (DER).
5. Part 2 – Further evaluate the clinical activity of GSK4524101 in combination with niraparib
6. Part 2 – Characterize PK or exposure of GSK4364973/GSK4524101 in combination with niraparib

Conditions and MedDRA coding

Neoplasms

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

" IPD plan description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf 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 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."

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. More than or equal to (≥)18 years of age
2. Eastern cooperative oncology group (ECOG) class 0-2
3. Life expectancy of a minimum of 3 month
4. Participant has histologically diagnosed advanced or metastatic solid tumor and has exhausted all standard of care treatment options (Part 1).
5. 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 6

1. Participant has not recovered (i.e., to Grade less than or equal to [≤1] or to baseline) from prior chemotherapy-induced AEs.
2. 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.
3. Participant has symptomatic uncontrolled brain or leptomeningeal metastases.
4. Participant has a known additional malignancy that progressed or required active treatment within the last 2 years
5. Participant has a known history of Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML).
6. Participant has uncontrolled hypertension with sustained systolic blood pressure (BP) >140 millimetres of mercury (mmHg) or diastolic BP >90 mmHg.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Part 1 - Proportion of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period
2. Part 1 - Proportion of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) based on Severity during DLT Observation Period
3. Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period
4. Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period
5. Part 1 - Percentage of Participants who require dosage interruptions, dose reductions, and drug discontinuations due to adverse reactions during DLT Observation Period
6. Part 2 - Confirmed Objective Response Rate (ORR)

Secondary endpoints 10

1. Part 1 - Area Under Curve (AUC), Time to Maximum Concentration, and half-life of GSK4364973
2. Part 1 and 2 - Maximum Concentration (Cmax) of GSK4364973
3. Part 1 and 2 - Plasma Concentration of Niraparib
4. Part 1 - Number of Participants with TEAEs and SAEs based on Severity beyond DLT Observation Period
5. Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period
6. Part 2 - Number of Participants with TEAEs and SAEs based on Severity
7. Part 2 - Duration of Treatment Emergent AEs and SAEs (Days)
8. Part 2 - Progression-free Survival (PFS)
9. Part 2 - Duration of Response (DOR)
10. Part 2 - Minimum Concentration (Cmin) of GSK4364973

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 10

Locations

8 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 186 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications