Neoplasms, Neoplasms, Colorectal
Conditions
Keywords
GSK5460025, 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 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.
Interventions
DRUGGSK5460025
GSK5460025 will be administered
Sponsors
GlaxoSmithKline
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level | 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 | Up to approximately 33 months | — |
| Part 1: Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period | Up to 28 days | — |
| Part 1: Number of participants with dosage modifications due to TEAEs per dose level | Up to approximately 33 months | — |
| Part 2: Objective Response Rate (ORR) | Up to approximately 33 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: Plasma concentrations for GSK5460025 | Up to approximately 36 months | — |
| Part 1: Area under the concentration-time curve (AUC) for GSK5460025 | Up to approximately 36 months | — |
| Part 1: Maximum concentration (Cmax) for GSK5460025 | Up to approximately 36 months | — |
| Part 1: Time to maximum concentration (Tmax) for GSK5460025 | 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 | Up to approximately 36 months | — |
| Part 2: Number of participants with TESAEs and TEAEs by severity | Up to approximately 36 months | — |
| Part 2: Number of participants with TEAEs leading to dosage modifications | Up to approximately 36 months | — |
| Part 2: Number of participants with clinically important changes in laboratory parameters, ECGs, and vital signs | Up to approximately 36 months | — |
| Part 2: Progression-free Survival (PFS) | Up to approximately 36 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 36 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 GSK5460025 | Up to approximately 36 months | — |
Countries
Canada, Denmark, France, Italy, Japan, Netherlands, Spain, Sweden, United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed