Clinical trial

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

Name

219590

Description

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).

Trial arms

Trial start

2023-10-24

Estimated PCD

2027-12-30

Trial end

2029-11-09

Status

Recruiting

Phase

Early phase I

Treatment

GSK4524101

GSK452101 will be administered.

Arms:

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

Niraparib

Niraparib will be administered.

Arms:

Part 1 - GSK4524101 plus Niraparib, Part 2 - GSK4524101 plus Niraparib, Part 2 - Niraparib

Size

135

Primary endpoint

Part 1 - Number of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period

Up to 28 days

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

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)

Up to approximately 52 weeks

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. 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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'This is an open-label non-blinded study'}}, 'enrollmentInfo': {'count': 135, 'type': 'ESTIMATED'}}

Updated at

2024-04-11

1 organization

2 products

1 abstract

1 indication

Organization

Product

Indication

Product

Abstract

First-in-human, phase 1/2 study of GSK4524101, an oral DNApolymerase theta inhibitor (POLQi), alone or combined with the poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) niraparib in adults with solid tumors.

Org: Stevenage, Uxbridge, Texas Oncology–San Antonio Babcock Next Oncology,