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

NCT07213609 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2240352025-522318-21
• Study Type: interventional
• Target: 47
• Locations: 3 countries
• Sites: 9

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.

Conditions

Neoplasms, Colorectal; Neoplasms

Keywords

GSK5460025; Solid tumors; Colon cancer; Rectal cancer; Colorectal cancer; Endometrial cancer; Mismatch repair deficient; dMMR; microsatellite instability high; MSI-H

Outcome Measures

Primary Outcomes (5)

• 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)

  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.

  Up to approximately 33 months

Secondary Outcomes (11)

• 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

Study Arms (2)

Part 1: Dose escalation of GSK5460025 monotherapy

EXPERIMENTAL

Participants will receive GSK5460025 as monotherapy.

Drug: GSK5460025

Part 2: Dose expansion of GSK5460025 monotherapy

EXPERIMENTAL

Participants will receive GSK5460025 as monotherapy.

Drug: GSK5460025

Interventions

GSK5460025 DRUG

GSK5460025 will be administered

Part 1: Dose escalation of GSK5460025 monotherapy; Part 2: Dose expansion of GSK5460025 monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Has histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor and has exhausted all standard of care treatment options
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (9)

GSK Investigational Site

Canton, Ohio, 44718, United States

RECRUITING

GSK Investigational Site

Nashville, Tennessee, 37203, United States

RECRUITING

GSK Investigational Site

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

GSK Investigational Site

Chiba, 277-8577, Japan

RECRUITING

GSK Investigational Site

Osaka, 573-1191, Japan

RECRUITING

GSK Investigational Site

Tokyo, 104-0045, Japan

RECRUITING

GSK Investigational Site

Tokyo, 135-8550, Japan

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Endometrial Neoplasms; Turcot syndrome

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: October 9, 2025
• Study Start: October 20, 2025
• Primary Completion (Estimated): September 28, 2028
• Study Completion (Estimated): October 27, 2028
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

Locations

JP (4); US (2); CA (3)