dMMR/MSI-H, advanced solid tumors
Conditions
Interventions
GSK5460025 will be administered
Part 1: Dose escalation of GSK5460025 monotherapy
Part 2: Dose expansion of GSK5460025 monotherapy
Sponsors
Ishibashi Hideyasu
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: -Number of participants with dose limiting toxicities (DLTs) per dose level -Number of participants with treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events (TEAEs) by severity per dose level -Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period -Number of participants with dosage modifications due to TEAEs per dose level Part 2: Objective Response Rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: -Plasma concentrations for GSK5460025 -Area under the concentration-time curve (AUC) for GSK5460025 -Maximum concentration (Cmax) for GSK5460025 -Time to maximum concentration (Tmax) for GSK5460025 -Number of participants with clinically important changes in laboratory parameters, Electrocardiogram (ECGs), and vital signs per dose level Part 2: -Number of participants with TESAEs and TEAEs by severity -Number of participants with TESAEs and TEAEs leading to dosage modifications by severity -Number of participants with clinically important changes in laboratory parameters, ECGs, and vital signs -Progression-free Survival (PFS) -Duration of Response (DoR) -Plasma concentration of GSK5460025 | — |
Countries
Canada, Japan, Netherlands, Spain, Sweden, United States
Contacts
Public ContactHideyasu Ishibashi
GlaxoSmithKline K.K.
Outcome results
None listed