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NCT07213609PHASE1, PHASE2Recruiting

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

GlaxoSmithKline

Start Date

10/20/2025

Completion Date

10/27/2028

Summary

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

GSK5460025

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Conditions

Neoplasms, ColorectalNeoplasms

Locations

GSK Investigational Site

Aurora, Colorado 80045

United States

GSK Investigational Site

Detroit, Michigan 48201

United States

GSK Investigational Site

Canton, Ohio 44718

United States

GSK Investigational Site

Nashville, Tennessee 37203

United States

GSK Investigational Site

Hamilton, Ontario L8V 5C2

Canada

GSK Investigational Site

Toronto, Ontario M5G 2M9

Canada

GSK Investigational Site

Montreal, Quebec H4A 3J1

Canada

GSK Investigational Site

Copenhagen, 2100

Denmark

GSK Investigational Site

Chiba, 277-8577

Japan

GSK Investigational Site

Osaka, 573-1191

Japan

GSK Investigational Site

Tokyo, 104-0045

Japan

GSK Investigational Site

Tokyo, 135-8550

Japan

GSK Investigational Site

Amsterdam, 1066 CX

Netherlands

GSK Investigational Site

Utrecht, 3584 CX

Netherlands

GSK Investigational Site

Barcelona, 08035

Spain

GSK Investigational Site

Madrid, 28034

Spain

GSK Investigational Site

Madrid, 28040

Spain

GSK Investigational Site

Madrid, 28041

Spain

GSK Investigational Site

Madrid, 28050

Spain

GSK Investigational Site

Lund, 22185

Sweden

GSK Investigational Site

Stockholm, 17164

Sweden

GSK Investigational Site

Uppsala, 751 85

Sweden