Mismatch Repair-deficient (dMMR) or Microsatellite Instability-High (MSI-H) solid tumor
Conditions
Interventions
Drug: GSK4418959
Drug:PD-1 inhibitor
Sponsors
Ishibashi Hideyasu
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Parts 1, 2, and 3 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 GSK4418959 (alone or in combination with PD-1 inhibitor, as determined between Investigator and sponsor) as next line of treatment -Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 -Is expected to have a minimum of 3 months life expectancy -Has adequate organ function, as defined in the protocol Parts 1 and 3 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: Parts 1, 2, and 3 exclusion criteria: -Has not recovered (i.e., to Grade -3, immune-related severe neurologic events of any grade, exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or Drug rash with eosinophilia and systemic signs syndrome [DRESS] syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary -Has any history of interstitial lung disease or pneumonitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1, Part 3: - Number of participants with dose limiting toxicities (DLTs) during DLT observation period, - Number of participants with treatment emergent adverse events (TEAEs) during DLT observation period, - Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs during DLT observation period Part 2: Objective Response Rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1, 2, 3 - Number of participants with TEAEs - Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs - Number of participants with clinical laboratory abnormalities Part 1, Part 3: - Area under the concentration-time curve (AUC) for GSK4418959, - Maximum concentration (Cmax) for GSK4418959, - Time to maximum concentration (Tmax) for GSK4418959, Part 2: - Progression-free Survival (PFS) - Duration of Response (DoR) - Plasma concentration of GSK4418959 | — |
Countries
Australia, Japan, United States
Contacts
Public ContactHideyasu Ishibashi
GlaxoSmithKline K.K.
Outcome results
None listed