Colon Cancer, Endometrial Cancer, Neoplasms, Colorectal, Rectal Cancer, Solid Tumor
Conditions
Keywords
GSK4418959, DNA Helicase Werner Inhibitor (WRNi), PD-1 inhibitor, Solid tumors, Colon cancer, Rectal cancer, Colorectal cancer, Endometrial cancer, Mismatch repair deficient, dMMR, microsatellite instability high, MSI-H
Brief 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 GSK4418959 alone or in combination with a PD-1 inhibitor agent can decrease tumor size, is safe, well-tolerated, and how amounts of the study drug decrease in the body over time.
Interventions
DRUGGSK4418959
GSK4418959 will be administered.
BIOLOGICALPD-1 inhibitor
PD-1 inhibitor will be administered.
Sponsors
GlaxoSmithKline
IDEAYA Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 0-2 * 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
Parts 1, 2, and 3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 3: Number of participants with dose limiting toxicities (DLTs) during DLT observation period | Up to 21 days | — |
| Part 1: Number of participants with treatment emergent adverse events (TEAEs) during DLT observation period | Up to 21 days | — |
| Part 1: Number of participants with dose limiting toxicities (DLTs) during DLT observation period | Up to 21 days | — |
| Part 3: Number of participants with treatment emergent adverse events (TEAEs) during DLT observation period | Up to 21 days | — |
| Part 1: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs during DLT observation period | Up to 21 days | — |
| Part 3: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs during DLT observation period | Up to 21 days | — |
| Part 2: Objective Response Rate (ORR) | Up to approximately 26 months | ORR is defined as percentage of participants with confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by investigator assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Area under the concentration-time curve (AUC) for GSK4418959 | From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months) | — |
| Part 1: Maximum concentration (Cmax) for GSK4418959 | From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months) | — |
| Part 1: Time to maximum concentration (Tmax) for GSK4418959 | From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months) | — |
| Part 3: AUC for GSK4418959 | From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months) | — |
| Part 3: Cmax for GSK4418959 | From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months) | — |
| Part 3: Tmax for GSK4418959 | From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months) | — |
| Part 1: Number of participants with TEAEs | Up to approximately 42 months | — |
| Part 2: Number of participants with TEAEs | Up to approximately 42 months | — |
| Part 3: Number of participants with TEAEs | Up to approximately 42 months | — |
| Part 1: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs | Up to approximately 42 months | — |
| Part 2: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs | Up to approximately 42 months | — |
| Part 3: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs | Up to approximately 42 months | — |
| Part 1: Number of participants with clinical laboratory abnormalities | Up to approximately 42 months | — |
| Part 2: Number of participants with clinical laboratory abnormalities | Up to approximately 42 months | — |
| Part 3: Number of participants with clinical laboratory abnormalities | Up to approximately 42 months | — |
| Part 2: Progression-free Survival (PFS) | Up to approximately 42 months | PFS is defined as time from first dose to progressive disease (as assessed per RECIST 1.1 by Investigator assessment) or death from any cause, whichever is earlier. |
| Part 2: Duration of Response (DoR) | Up to approximately 42 months | DoR is defined as time from first documented PR or CR to progressive disease (as assessed per RECIST 1.1 by investigator assessment) or death from any cause, whichever is earlier for participants who have achieved a confirmed CR or PR. |
| Part 2: Plasma concentration of GSK4418959 | From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months) | — |
Countries
Australia, Belgium, Japan, Netherlands, South Korea, Spain, United States
Outcome results
None listed