Phase 1/2 study to investigate the safety and preliminary efficacy of GSK5460025 alone or in combination with other anti-cancer agents in dMMR/MSI-H solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pharma R&D

External identifiers

EU CT number

2025-522318-21-00

ClinicalTrials.gov

NCT07213609

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

"Part 1: Determine the safety and tolerability, and the recommended dose for expansion (RDE) and/or maximum tolerated dose (MTD) for GSK5460025 as monotherapy
Part 2: Evaluate the preliminary anti-tumor activity of GSK5460025 as monotherapy in Colorectal cancer (CRC) and, separately, Endometrial cancer (EC)
"

Secondary objectives 4

1. Characterize the Pharmacokinetic(s) (PK) properties of GSK5460025 as monotherapy
2. Part 1: Further assess the safety and tolerability of GSK5460025 as monotherapy
3. Part 2: Further evaluate the safety and tolerability of GSK5460025 monotherapy administered at the RDE in CRC and/or EC
4. Part 2: Further evaluate the anti-tumor activity of GSK5460025 as monotherapy in participants with advanced Mismatch repair deficient (dMMR)/ Microsatellite Instability-High (MSI-H) CRC and separately, advanced dMMR/MSI-H EC

Conditions and MedDRA coding

Neoplasms, Colorectal

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participant is at least 18 years of age.
2. Participant has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor.
3. Participant 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.
4. Participant provides an archival or fresh (preferred) formalin fixed, paraffin embedded (FFPE) sample.
5. Participant intends to receive GSK5460025 (as described in the protocol) as next treatment.
6. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
7. Participant is expected to have a minimum of 3 months life expectancy.
8. Participant has adequate organ function, as defined in the protocol.
9. Part 1: Participant has histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor and has exhausted all standard of care treatment options.
10. Part 2: Participant has histologically diagnosed advanced (unresectable, metastatic or recurrent) Colorectal cancer (CRC) or Endometrial cancer (EC).
11. Part 2: Participant 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.
12. Part 2: Participant 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 8

1. Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced Adverse Events (AEs).
2. Participant has received prior treatment with a Werner (WRN) inhibitor or Nucleotide Excision Repair Targeting (NERT) agent.
3. Participant is unable to swallow and retain orally administered study treatment.
4. Participant has untreated or progressed metastases in brain or CNS.
5. Participant 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.
6. Participant has any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs.
7. Participant has cirrhosis or current unstable liver or biliary disease.
8. Participant has known hypersensitivity to any of the study interventions or any of their excipients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level
2. Part 1: Number of participants with treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events (TEAEs) by severity per dose level
3. Part 1: Duration of TESAEs and TEAEs per dose level
4. Part 1: Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period
5. Part 1: Number of participants with dosage modifications due to TEAEs per dose level
6. "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."

Secondary endpoints 10

1. Part 1: Plasma concentrations for GSK5460025
2. Part 1: Area under the concentration-time curve (AUC) for GSK5460025
3. Part 1: Time to maximum concentration (Tmax) for GSK5460025
4. Part 1: Number of participants with clinically important changes in laboratory parameters, Electrocardiogram (ECGs), and vital signs per dose level
5. Part 2: Number of participants with TESAEs and TEAEs by severity
6. Part 2: Number of participants with TEAEs leading to dosage modifications
7. Part 2: Number of participants with clinically important changes in laboratory parameters, ECGs, and vital signs
8. 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
9. 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.
10. Part 2: Plasma concentration of GSK5460025

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 15

Locations

6 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 65 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications