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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06077877
• Other study ID #: 219590
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 24, 2023
• Est. completion date: November 9, 2029

Study information

• Verified date: April 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: November 9, 2029
• Est. primary completion date: December 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• GSK4524101
GSK452101 will be administered.
• Niraparib
Niraparib will be administered.

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Fairfax	Virginia
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 - Number of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period		Up to 28 days
Primary	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
Primary	Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period		Up to 28 days
Primary	Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period		Up to 28 days
Primary	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
Primary	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	Part 1 - Area Under Curve (AUC) of GSK4364973 (Metabolite of GSK4524101)		Up to 21 weeks
Secondary	Part 1 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)		Up to 21 weeks
Secondary	Part 1 - Time to Maximum Concentration of GSK4364973 (Metabolite of GSK4524101)		Up to 21 weeks
Secondary	Part 1 - Half-life of GSK4364973 (Metabolite of GSK4524101) (Days)		Up to 21 weeks
Secondary	Part 1 -Plasma Concentration of Niraparib		Up to 21 weeks
Secondary	Part 1 - Number of Participants with TEAEs and SAEs based on Severity beyond DLT Observation Period		Up to approximately 24 weeks
Secondary	Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period		Up to approximately 24 weeks
Secondary	Part 2 - Number of Participants with TEAEs and SAEs based on Severity		Up to approximately 52 weeks
Secondary	Part 2 - Duration of Treatment Emergent AEs and SAEs (Days)		Up to approximately 52 weeks
Secondary	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
Secondary	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
Secondary	Part 2 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)		Up to 21 weeks
Secondary	Part 2 - Minimum Concentration (Cmin) of GSK4364973 (Metabolite of GSK4524101)		Up to 21 weeks
Secondary	Part 2 -Plasma Concentration of Niraparib		Up to 21 weeks