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

Study Identifier:
224035
CT.gov Identifier:
NCT07213609
EudraCT Identifier:
2025-522318-21
EU Trial (CTIS) Number:
N/A
Study Contact Information:
N/A
Recruiting

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Study 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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Bowel (Colorectal)
Solid Tumor
Endometrial
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: EXPERIMENTAL: Part 1: Dose escalation of GSK5460025 monotherapy
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Drug: Participants will receive GSK5460025 as monotherapy.
Drug: Drug: GSK5460025
Drug: GSK5460025 will be administered
Drug: EXPERIMENTAL: Part 2: Dose expansion of GSK5460025 monotherapy
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
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

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Emiliano Calvo
Status
Will Be Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)
Solid Tumor
Endometrial
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Victor Moreno Garcia
Status
Will Be Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)
Solid Tumor
Endometrial