GSK5460025 alone or with other anti-cancer drugs for advanced solid tumors

A Phase 1/2 Open-label, Multicenter Study of Oral GSK5460025 Alone or in Combination With Other Anti-cancer Agents in Adult Participants With Mismatch Repair-deficient (dMMR) or Microsatellite Instability-High (MSI-H) Solid Tumors

This trial will test whether the experimental drug GSK5460025, alone or combined with other cancer medicines, can shrink tumors and be safe for people with advanced colorectal or other solid tumors that are dMMR/MSI-H or have unknown MMR/MSI status.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: GlaxoSmithKline (industry)
• Locations: 9 sites (Canton, Ohio and 8 other locations)
• Trial ID: NCT07213609 on ClinicalTrials.gov

What this trial studies

This is a Phase 1/2, early-stage interventional trial testing GSK5460025 as a single agent and in combination with other anti-cancer therapies to characterize safety, tolerability, preliminary anti-tumor activity, and how the drug is processed in the body. Participants must have advanced (unresectable, metastatic, or recurrent) solid tumors and either known dMMR/MSI-H status or provide tissue for central MMR/MSI testing. The study requires archival or fresh tumor samples, an ECOG performance status of 0–2, adequate organ function, and an expectation of at least three months' life expectancy. Dose-escalation and expansion cohorts are used to identify tolerable doses and to observe early signals of tumor shrinkage.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced, unresectable or metastatic solid tumors (including colorectal cancer) who have exhausted standard therapies, have dMMR/MSI-H or will undergo MMR/MSI testing, can provide tumor tissue, and have ECOG 0–2 and adequate organ function.

Not a fit: People whose tumors lack the dMMR/MSI-H feature or who are medically unfit for treatment (for example poor organ function, ECOG >2, or life expectancy under three months) are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, GSK5460025 could provide a new treatment option that shrinks tumors in people with dMMR/MSI-H or related advanced solid tumors.

How similar studies have performed: Other therapies targeting dMMR/MSI-H tumors (notably immune checkpoint inhibitors) have shown clinical benefit, but GSK5460025 is a novel agent and its safety and effectiveness are unproven.

Eligibility 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:

* 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

Where this trial is running

Canton, Ohio and 8 other locations

• GSK Investigational Site — Canton, Ohio, United States (RECRUITING)
• GSK Investigational Site — Nashville, Tennessee, United States (RECRUITING)
• GSK Investigational Site — Hamilton, Ontario, Canada (RECRUITING)
• GSK Investigational Site — Toronto, Ontario, Canada (RECRUITING)
• GSK Investigational Site — Montreal, Quebec, Canada (RECRUITING)
• GSK Investigational Site — Chiba, Japan (RECRUITING)
• GSK Investigational Site — Osaka, Japan (RECRUITING)
• GSK Investigational Site — Tokyo, Japan (RECRUITING)
• GSK Investigational Site — Tokyo, Japan (RECRUITING)

Study contacts

• Study coordinator: US GSK Clinical Trials Call Center

Conditions: Neoplasms, Colorectal, Neoplasms, GSK5460025, Solid tumors, Colon cancer, Rectal cancer, Colorectal cancer, Endometrial cancer