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

GlaxoSmithKline (GSK)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Neoplasms; Neoplasms, Colorectal

Treatments: Drug: GSK5460025

Study type: Interventional

Funder types: Industry

Identifiers

NCT07213609

224035

2025-522318-21 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 47 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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47 participants in 2 patient groups

Part 1: Dose escalation of GSK5460025 monotherapy

Experimental group

Description:

Participants will receive GSK5460025 as monotherapy.

Treatment:

Drug: GSK5460025

Part 2: Dose expansion of GSK5460025 monotherapy

Experimental group

Description:

Participants will receive GSK5460025 as monotherapy.

Treatment:

Drug: GSK5460025