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
- Conditions
- Neoplasms, Colorectal
- Interventions
- Drug: GSK5460025
- Registration Number
- NCT07213609
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 47
- 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 (alone or in combination with other anti-cancer agents, as described in the protocol) 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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Dose escalation of GSK5460025 monotherapy GSK5460025 Participants will receive GSK5460025 as monotherapy. Part 2: Dose expansion of GSK5460025 monotherapy GSK5460025 Participants will receive GSK5460025 as monotherapy.
- Primary Outcome Measures
Name Time Method 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: Duration of TESAEs and TEAEs 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: Duration of TESAEs and TEAEs 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 Outcome Measures
Name Time Method 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: Duration of TESAEs and TEAEs Up to approximately 36 months Part 2: Number of participants with TESAEs and TEAEs leading to dosage modifications by severity Up to approximately 36 months Part 2: Duration of TESAEs and 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