Last updated: 12/19/2025 16:30:43
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
GSK study ID
224035
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Recruiting
Recruiting
Trial overview
Official title: 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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level
Timeframe: 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
Timeframe: Up to approximately 33 months
Part 1: Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period
Timeframe: Up to 28 days
Part 1: Number of participants with dosage modifications due to TEAEs per dose level
Timeframe: Up to approximately 33 months
Part 2: Objective Response Rate (ORR)
Timeframe: Up to approximately 33 months
Secondary outcomes:
Part 1: Plasma concentrations for GSK5460025
Timeframe: Up to approximately 36 months
Part 1: Area under the concentration-time curve (AUC) for GSK5460025
Timeframe: Up to approximately 36 months
Part 1: Maximum concentration (Cmax) for GSK5460025
Timeframe: Up to approximately 36 months
Part 1: Time to maximum concentration (Tmax) for GSK5460025
Timeframe: 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
Timeframe: Up to approximately 36 months
Part 2: Number of participants with TESAEs and TEAEs by severity
Timeframe: Up to approximately 36 months
Part 2: Number of participants with TEAEs leading to dosage modifications
Timeframe: Up to approximately 36 months
Part 2: Number of participants with clinically important changes in laboratory parameters, ECGs, and vital signs
Timeframe: Up to approximately 36 months
Part 2: Progression-free Survival (PFS)
Timeframe: Up to approximately 36 months
Part 2: Duration of Response (DoR)
Timeframe: Up to approximately 36 months
Part 2: Plasma concentration of GSK5460025
Timeframe: Up to approximately 36 months
Interventions:
Enrollment:
47
Primary completion date:
2028-28-09
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms, Colorectal, Neoplasms
Product
Not applicable
Collaborators
Not applicable
Study date(s)
October 2025 to October 2028
Type
Interventional
Phase
1/2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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
Has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor
Exclusion criteria:
- 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
Has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced Adverse Events (AEs)
Trial location(s)
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Recruiting
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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