A Study to Investigate the Safety and Preliminary Efficacy of GSK5460025 Alone or in Combination With Other Anti-cancer Agents in Participants With Solid Tumors

June 17, 2026 updated by: GlaxoSmithKline

A Phase 1/2 Open-label, Multicenter Study of Oral GSK5460025 Alone or in Combination With Other Anti-cancer Agents in Adult Participants With Mismatch Repair-deficient (dMMR) or Microsatellite Instability-High (MSI-H) Solid Tumors

Solid tumours are abnormal lumps of tissue that can occur in different parts of the body. The tumours involved in this study have specific genetic characteristics that can make them more aggressive and challenging to treat. The study will test whether GSK5460025 alone or in combination (potential combinations may be included in future amendments to the protocol) with other anti-cancer agents can decrease tumor size, is safe, well-tolerated, and how the drug is processed in the body over time.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

47

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Courtney Coschi
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Abdulazeez Salawu
        • Contact:
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Xing Zeng
  • Japan
      • Chiba, Japan, 277-8577
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Shigehiro Koganemaru
      • Osaka, Japan, 573-1191
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Toshio Shimizu
      • Tokyo, Japan, 104-0045
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Noboru Yamamoto
        • Contact:
        • Contact:
      • Tokyo, Japan, 135-8550
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Shigehisa Kitano
        • Contact:
        • Contact:
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Marieke Vollebergh
  • Spain
      • Madrid, Spain, 28034
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Federico Longo Muñoz
      • Madrid, Spain, 28040
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Victor Moreno
        • Contact:
        • Contact:
      • Madrid, Spain, 28041
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jorge Barriuso Feijoo
      • Madrid, Spain, 28050
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Emiliano Calvo Aller
        • Contact:
        • Contact:
  • Sweden
      • Lund, Sweden, 22185
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ana Carneiro
      • Stockholm, Sweden, 17164
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lisa Liu Burstrom
      • Uppsala, Sweden, 751 85
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Simon Pahnke
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jill Alldredge
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Wasif Saif
    • Ohio
      • Canton, Ohio, United States, 44718
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nashat Gabrail
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Deepak Bhamidipati

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor
  • Has a known dMMR/MSI-H status as determined by a certified local laboratory at the time of Pre-screening or has an unknown Mismatch repair (MMR)/ Microsatellite Instability (MSI) status at the time of Pre-screening and MMR/MSI status will be determined by central reference laboratory
  • Provides an archival or fresh (preferred) formalin fixed, paraffin embedded (FFPE) sample
  • Intends to receive GSK5460025 as next treatment
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Is expected to have a minimum of 3 months life expectancy
  • Has adequate organ function, as defined in the protocol

Part 1 inclusion criteria:

• Has histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor and has exhausted all standard of care treatment options

Part 2 inclusion criteria:

  • Has histologically diagnosed advanced (unresectable, metastatic or recurrent) Colorectal cancer (CRC) or Endometrial cancer (EC)
  • Has received at least 1 but no more than 3 lines of systemic anticancer therapy for their advanced (unresectable, metastatic or recurrent) disease including at least one line of Immune checkpoint inhibitors (ICI) therapy
  • Has measurable disease (i.e., at least 1 target lesion) during the Screening period per RECIST 1.1, as determined by the investigator

Exclusion Criteria:

  • Has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced Adverse Events (AEs)
  • Has received prior treatment with a Werner (WRN) inhibitor or Nucleotide Excision Repair Targeting (NERT) agent.
  • Is unable to swallow and retain orally administered study treatment
  • Has untreated or progressed metastases in brain or CNS
  • Has a known additional malignancy that progressed or required active treatment within the last 2 years because reoccurrence of another malignancy would confound interpretation by RECIST 1.1 criteria. Exceptions include basal or squamous cell carcinomas of the skin or in situ carcinomas [e.g., breast, cervix, bladder] that have been resected with no evidence of metastatic disease.
  • Has any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs
  • Has cirrhosis or current unstable liver or biliary disease
  • Has known hypersensitivity to any of the study interventions or any of their excipients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1: Dose escalation of GSK5460025 monotherapy
Participants will receive GSK5460025 as monotherapy.
Drug: GSK5460025
GSK5460025 will be administered
Experimental: Part 2: Dose expansion of GSK5460025 monotherapy
Participants will receive GSK5460025 as monotherapy.
Drug: GSK5460025
GSK5460025 will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level
Time Frame: Up to 28 days
Up to 28 days
Part 1: Number of participants with treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events (TEAEs) by severity per dose level
Time Frame: Up to approximately 33 months
Up to approximately 33 months
Part 1: Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period
Time Frame: Up to 28 days
Up to 28 days
Part 1: Number of participants with dosage modifications due to TEAEs per dose level
Time Frame: Up to approximately 33 months
Up to approximately 33 months
Part 2: Objective Response Rate (ORR)
Time Frame: Up to approximately 33 months
ORR is defined as percentage of participants with confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by investigator assessment.
Up to approximately 33 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Plasma concentrations for GSK5460025
Time Frame: Up to approximately 36 months
Up to approximately 36 months
Part 1: Area under the concentration-time curve (AUC) for GSK5460025
Time Frame: Up to approximately 36 months
Up to approximately 36 months
Part 1: Maximum concentration (Cmax) for GSK5460025
Time Frame: Up to approximately 36 months
Up to approximately 36 months
Part 1: Time to maximum concentration (Tmax) for GSK5460025
Time Frame: Up to approximately 36 months
Up to approximately 36 months
Part 1: Number of participants with clinically important changes in laboratory parameters, Electrocardiogram (ECGs), and vital signs per dose level
Time Frame: Up to approximately 36 months
Up to approximately 36 months
Part 2: Number of participants with TESAEs and TEAEs by severity
Time Frame: Up to approximately 36 months
Up to approximately 36 months
Part 2: Number of participants with clinically important changes in laboratory parameters, ECGs, and vital signs
Time Frame: Up to approximately 36 months
Up to approximately 36 months
Part 2: Progression-free Survival (PFS)
Time Frame: Up to approximately 36 months
PFS is defined as time from first dose to progressive disease (as assessed per RECIST 1.1 by Investigator assessment) or death from any cause, whichever is earlier
Up to approximately 36 months
Part 2: Duration of Response (DoR)
Time Frame: Up to approximately 36 months
DoR is defined as time from first documented PR or CR to progressive disease (as assessed per RECIST 1.1 by investigator assessment) or death from any cause, whichever is earlier for participants who have achieved a confirmed CR or PR.
Up to approximately 36 months
Part 2: Plasma concentration of GSK5460025
Time Frame: Up to approximately 36 months
Up to approximately 36 months
Part 2: Number of participants with TEAEs leading to dosage modifications
Time Frame: Up to approximately 36 months
Up to approximately 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2025

Primary Completion (Estimated)

September 28, 2028

Study Completion (Estimated)

October 27, 2028

Study Registration Dates

First Submitted

July 4, 2025

First Submitted That Met QC Criteria

October 2, 2025

First Posted (Actual)

October 9, 2025

Study Record Updates

Last Update Posted (Actual)

June 18, 2026

Last Update Submitted That Met QC Criteria

June 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 224035
  • 2025-522318-21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data 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 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 asset(s) with development terminated across all indications.

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 Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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