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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06077877
Recruitment Status : Recruiting
First Posted : October 11, 2023
Last Update Posted : April 11, 2024
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE October 5, 2023
First Posted Date  ICMJE October 11, 2023
Last Update Posted Date April 11, 2024
Actual Study Start Date  ICMJE October 24, 2023
Estimated Primary Completion Date December 30, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2023)
  • Part 1 - Number of Participants with Dose Limiting Toxicities (DLTs) during DLT Observation Period [ Time Frame: 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 [ Time Frame: Up to 28 days ]
  • Part 1 - Duration of Treatment Emergent AEs and SAEs (Days) during DLT Observation Period [ Time Frame: Up to 28 days ]
  • Part 1 - Percentage of Participants who receive all Planned Doses during DLT Observation Period [ Time Frame: 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 [ Time Frame: Up to 28 days ]
  • Part 2 - Confirmed Objective Response Rate (ORR) [ Time Frame: Up to approximately 52 weeks ]
    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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2023)
  • Part 1 - Area Under Curve (AUC) of GSK4364973 (Metabolite of GSK4524101) [ Time Frame: Up to 21 weeks ]
  • Part 1 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101) [ Time Frame: Up to 21 weeks ]
  • Part 1 - Time to Maximum Concentration of GSK4364973 (Metabolite of GSK4524101) [ Time Frame: Up to 21 weeks ]
  • Part 1 - Half-life of GSK4364973 (Metabolite of GSK4524101) (Days) [ Time Frame: Up to 21 weeks ]
  • Part 1 -Plasma Concentration of Niraparib [ Time Frame: Up to 21 weeks ]
  • Part 1 - Number of Participants with TEAEs and SAEs based on Severity beyond DLT Observation Period [ Time Frame: Up to approximately 24 weeks ]
  • Part 1 - Duration of TEAEs and SAEs (Days) beyond DLT Observation Period [ Time Frame: Up to approximately 24 weeks ]
  • Part 2 - Number of Participants with TEAEs and SAEs based on Severity [ Time Frame: Up to approximately 52 weeks ]
  • Part 2 - Duration of Treatment Emergent AEs and SAEs (Days) [ Time Frame: Up to approximately 52 weeks ]
  • Part 2 - Progression-free Survival (PFS) [ Time Frame: Up to approximately 52 weeks ]
    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
  • Part 2 - Duration of Response (DOR) [ Time Frame: Up to approximately 52 weeks ]
    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
  • Part 2 -Maximum Concentration (Cmax) of GSK4364973 (Metabolite of GSK4524101) [ Time Frame: Up to 21 weeks ]
  • Part 2 - Minimum Concentration (Cmin) of GSK4364973 (Metabolite of GSK4524101) [ Time Frame: Up to 21 weeks ]
  • Part 2 -Plasma Concentration of Niraparib [ Time Frame: Up to 21 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description:
This is an open-label non-blinded study
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: GSK4524101
    GSK452101 will be administered.
  • Drug: Niraparib
    Niraparib will be administered.
Study Arms  ICMJE
  • Experimental: Part 1 - GSK4524101 Monotherapy
    Intervention: Drug: GSK4524101
  • Experimental: Part 1 - GSK4524101 plus Niraparib
    Interventions:
    • Drug: GSK4524101
    • Drug: Niraparib
  • Experimental: Part 1 - GSK4524101 Food Effect Cohort
    Intervention: Drug: GSK4524101
  • Experimental: Part 2 - GSK4524101 plus Niraparib
    Interventions:
    • Drug: GSK4524101
    • Drug: Niraparib
  • Active Comparator: Part 2 - Niraparib
    Intervention: Drug: Niraparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 15, 2023)		 135
Original Estimated Enrollment  ICMJE
 (submitted: October 5, 2023)		 112
Estimated Study Completion Date  ICMJE November 9, 2029
Estimated Primary Completion Date December 30, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06077877
Other Study ID Numbers  ICMJE 219590
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (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.
URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
Current Responsible Party GlaxoSmithKline
Original Responsible Party Same as current
Current Study Sponsor  ICMJE GlaxoSmithKline
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP