Clinical trial NCT06077877: A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Anticancer Activity of GSK4524101 Alone or With Niraparib in Participants With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neoplasms
Keywords: POLQi
Niraparib
GSK4524101
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2023-10-11
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1 - Proportion of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period
timeFrame: Up to 28 days
measure: Part 1 - Proportion of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) based on Severity during DLT Observation Period
timeFrame: Up to 28 days
measure: Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period
timeFrame: Up to 28 days
measure: Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period
timeFrame: Up to 28 days
measure: Part 1 -Percentage of Participants who require dosage interruptions, dose reductions, and drug discontinuations due to adverse reactions during DLT Observation Period
timeFrame: Up to 28 days
measure: Part 2 - Confirmed Objective Response Rate (ORR)
timeFrame: Up to approximately 52 weeks
Secondary outcomes:
measure: Part 1 - Area Under Curve (AUC) of GSK4364973 (Metabolite of GSK4524101)
timeFrame: Up to 21 weeks
measure: Part 1 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)
timeFrame: Up to 21 weeks
measure: Part 1 - Time to Maximum Concentration of GSK4364973 (Metabolite of GSK4524101)
timeFrame: Up to 21 weeks
measure: Part 1 - Half-life of GSK4364973 (Metabolite of GSK4524101) (Days)
timeFrame: Up to 21 weeks
measure: Part 1 -Plasma Concentration of Niraparib
timeFrame: Up to 21 weeks
measure: Part 1 - Number of Participants with TEAEs and SAEs based on Severity beyond DLT Observation Period
timeFrame: Up to approximately 24 weeks
measure: Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period
timeFrame: Up to approximately 24 weeks
measure: Part 2 - Number of Participants with TEAEs and SAEs based on Severity
timeFrame: Up to approximately 52 weeks
measure: Part 2 - Duration of Treatment Emergent AEs and SAEs (Days)
timeFrame: Up to approximately 52 weeks
measure: Part 2 - Progression-free Survival (PFS)
timeFrame: Up to approximately 52 weeks
measure: Part 2 - Duration of Response (DOR)
timeFrame: Up to approximately 52 weeks
measure: Part 2 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101)
timeFrame: Up to 21 weeks
measure: Part 2 - Minimum Concentration (Cmin) of GSK4364973 (Metabolite of GSK4524101)
timeFrame: Up to 21 weeks
measure: Part 2 -Plasma Concentration of Niraparib
timeFrame: Up to 21 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Fairfax
country: United States
facility: GSK Investigational Site
state: Virginia
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: