Clinical trial • Phase I/II • Oncology
GSK5460025A for Colorectal cancer | Endometrial cancer | dMMR/MSI-H solid tumours
Phase I/II trial of GSK5460025A for Colorectal cancer | Endometrial cancer | dMMR/MSI-H solid tumours. open-label, none/not specified-controlled, adaptive.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Colorectal cancer | Endometrial cancer | dMMR/MSI-H solid tumours
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 04-12-2025
- First CTIS Authorization Date
- 14-04-2026
Trial design
open-label, none/not specified-controlled, adaptive Phase I/II trial across 16 sites in France, Italy, Spain and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Adaptive
- True, Part 1 is a dose-escalation (adaptive) design to determine safety/tolerability and RDE and/or MTD for GSK5460025 (DLT observation and dose-escalation rules described in protocol).
- Biomarker Stratified
- True, biomarker: dMMR/MSI-H status
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 20
Eligibility
Recruits 20 Vulnerable population selected (isVulnerablePopulationSelected = true). Participants are adults (≥18 years). Informed consent handled via subject information and ICF documents (multiple L1_ICF Main/Pre-screening/Pregnancy/Genetic forms) and eICF via Medable digital health platform (eICF screenshots and privacy notice present). No paediatric assent documents provided in the record..
- Vulnerable Population
- Vulnerable population selected (isVulnerablePopulationSelected = true). Participants are adults (≥18 years). Informed consent handled via subject information and ICF documents (multiple L1_ICF Main/Pre-screening/Pregnancy/Genetic forms) and eICF via Medable digital health platform (eICF screenshots and privacy notice present). No paediatric assent documents provided in the record.
Inclusion criteria
- {"criterion_text":"- Participant is at least 18 years of age.\n- Part 2: Participant has histologically diagnosed advanced (unresectable, metastatic or recurrent) Colorectal cancer (CRC) or Endometrial cancer (EC).\n- 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.\n- 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.\n- Participant has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor.\n- 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.\n- Participant provides an archival or fresh (preferred) formalin fixed, paraffin embedded (FFPE) sample.\n- Participant intends to receive GSK5460025 (as described in the protocol) as next treatment.\n- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n- Participant is expected to have a minimum of 3 months life expectancy.\n- Participant has adequate organ function, as defined in the protocol.\n- Part 1: Participant has histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor and has exhausted all standard of care treatment options."}
Exclusion criteria
- {"criterion_text":"- Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced Adverse Events (AEs).\n- Participant has received prior treatment with a Werner (WRN) inhibitor or Nucleotide Excision Repair Targeting (NERT) agent.\n- Participant is unable to swallow and retain orally administered study treatment.\n- Participant has untreated or progressed metastases in brain or CNS.\n- 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.\n- Participant has any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs.\n- Participant has cirrhosis or current unstable liver or biliary disease.\n- Participant has known hypersensitivity to any of the study interventions or any of their excipients."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Number of participants with treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events (TEAEs) by severity per dose level","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Duration of TESAEs and TEAEs per dose level","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Number of participants with dosage modifications due to TEAEs per dose level","definition_or_measurement_approach":""}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"ORR defined as percentage of participants with confirmed CR or PR per RECIST 1.1 by investigator assessment."}
Secondary endpoints
- {"endpoint_text":"- Part 1: Plasma concentrations for GSK5460025","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Area under the concentration-time curve (AUC) for GSK5460025","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Time to maximum concentration (Tmax) for GSK5460025","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Number of participants with clinically important changes in laboratory parameters, Electrocardiogram (ECGs), and vital signs per dose level","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 2: Number of participants with TESAEs and TEAEs by severity","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 2: Number of participants with TEAEs leading to dosage modifications","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 2: Number of participants with clinically important changes in laboratory parameters, ECGs, and vital signs","definition_or_measurement_approach":""}
- {"endpoint_text":"- 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","definition_or_measurement_approach":"PFS defined as time from first dose to progressive disease per RECIST 1.1 (investigator) or death from any cause, whichever earlier."}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"DoR defined as time from first documented PR or CR to progressive disease per RECIST 1.1 (investigator) or death, whichever earlier, for participants with confirmed CR or PR."}
- {"endpoint_text":"- Part 2: Plasma concentration of GSK5460025","definition_or_measurement_approach":""}
Recruitment
- Digital Remote Recruitment
- True, eICF and digital health platform use via Medable (eICF screenshots and privacy notice available)
- Planned Sample Size
- 27
- Recruitment Window Months
- 29
- Consent Approach
- Informed consent obtained via subject information and ICF documents (L1_ICF Main, Pre-screening, Pregnancy, Genetic forms). eICF implemented via Medable digital health platform (screenshots and privacy notice provided). Consent provided by participant (>=18).
Geography
- Total Number Of Sites
- 16
- Total Number Of Participants
- 27
France
- Earliest CTIS Part Ii Submission Date
- 26-03-2026
- Latest Decision Or Authorization Date
- 14-04-2026
- Processing Time Days
- 19
- Number Of Sites
- 3
- Number Of Participants
- 7
Sites
- Site Name
- Centre Leon Berard
- Department Name
- Medical Oncology
- Principal Investigator Name
- Isabelle RAY-COQUARD
- Principal Investigator Email
- isabelle.ray-coquard@lyon.unicancer.fr
- Contact Person Name
- Isabelle RAY-COQUARD
- Contact Person Email
- isabelle.ray-coquard@lyon.unicancer.fr
- Site Name
- Institut De Cancerologie De L Ouest
- Department Name
- Medical Oncology
- Principal Investigator Name
- Jean-Sébastien FRENEL
- Principal Investigator Email
- jean-sebastien.frenel@ico.unicancer.fr
- Contact Person Name
- Jean-Sébastien FRENEL
- Contact Person Email
- jean-sebastien.frenel@ico.unicancer.fr
- Site Name
- Institut Gustave Roussy
- Department Name
- DITEP Drug Development Department
- Principal Investigator Name
- Antoine Hollebecque
- Principal Investigator Email
- antoine.hollebecque@gustaveroussy.fr
- Contact Person Name
- Antoine Hollebecque
- Contact Person Email
- antoine.hollebecque@gustaveroussy.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 26-03-2026
- Latest Decision Or Authorization Date
- 16-04-2026
- Processing Time Days
- 21
- Number Of Sites
- 2
- Number Of Participants
- 2
Sites
- Site Name
- ASST Grande Ospedale Metropolitano Niguarda
- Department Name
- Unità Clinica SC Oncologia Falck
- Principal Investigator Name
- Salvatore Siena
- Principal Investigator Email
- salvatore.siena@ospedaleniguarda.it
- Contact Person Name
- Salvatore Siena
- Contact Person Email
- salvatore.siena@ospedaleniguarda.it
- Site Name
- Istituto Europeo Di Oncologia S.r.l.
- Department Name
- Divisione Sviluppo di Nuovi Farmaci per Terapie Innovative
- Principal Investigator Name
- Giuseppe Curigliano
- Principal Investigator Email
- giuseppe.curigliano@ieo.it
- Contact Person Name
- Giuseppe Curigliano
- Contact Person Email
- giuseppe.curigliano@ieo.it
Spain
- Earliest CTIS Part Ii Submission Date
- 25-03-2026
- Latest Decision Or Authorization Date
- 15-04-2026
- Processing Time Days
- 21
- Number Of Sites
- 5
- Number Of Participants
- 7
Sites
- Site Name
- Hospital Universitario Hm Sanchinarro
- Department Name
- Oncología
- Principal Investigator Name
- Emiliano Calvo Aller
- Principal Investigator Email
- emiliano.calvo@startmadrid.com
- Contact Person Name
- Emiliano Calvo Aller
- Contact Person Email
- emiliano.calvo@startmadrid.com
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Oncología
- Principal Investigator Name
- Jorge Barriuso Feijoo
- Principal Investigator Email
- jorge.barriuso.imas12@h12o.es
- Contact Person Name
- Jorge Barriuso Feijoo
- Contact Person Email
- jorge.barriuso.imas12@h12o.es
- Site Name
- Hospital Universitario Ramon Y Cajal
- Department Name
- Oncología
- Principal Investigator Name
- Federico Longo Muñóz
- Principal Investigator Email
- federico.longo@salud.madrid.org
- Contact Person Name
- Federico Longo Muñóz
- Contact Person Email
- federico.longo@salud.madrid.org
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncología
- Principal Investigator Name
- Victoria Sánchez Pérez
- Principal Investigator Email
- victoriasanchez@vhio.net
- Contact Person Name
- Victoria Sánchez Pérez
- Contact Person Email
- victoriasanchez@vhio.net
- Site Name
- Hospital Universitario Fundacion Jimenez Diaz
- Department Name
- Oncología
- Principal Investigator Name
- Víctor Moreno Garcia
- Principal Investigator Email
- victor.moreno@startmadrid.com
- Contact Person Name
- Víctor Moreno Garcia
- Contact Person Email
- victor.moreno@startmadrid.com
Sweden
- Earliest CTIS Part Ii Submission Date
- 23-02-2026
- Latest Decision Or Authorization Date
- 15-04-2026
- Processing Time Days
- 51
- Number Of Sites
- 3
- Number Of Participants
- 5
Sites
- Site Name
- Uppsala University Hospital
- Department Name
- KFUE - Kliniska forsknings- och utvecklingsenheten,Blod- och Tumörsjukdomar
- Principal Investigator Name
- Simon Pahnke
- Principal Investigator Email
- kliniskaprovningar@akademiska.se
- Contact Person Name
- Simon Pahnke
- Contact Person Email
- kliniskaprovningar@akademiska.se
- Site Name
- Karolinska University Hospital
- Department Name
- Centrum för Kliniska Cancerstudier Tema Cancer
- Principal Investigator Name
- Lisa Liu Burström
- Principal Investigator Email
- firstname.lastname@regionstockholm.se
- Contact Person Name
- Lisa Liu Burström
- Contact Person Email
- firstname.lastname@regionstockholm.se
- Site Name
- Region Skane Skanes Universitetssjukhus
- Department Name
- Onkologiska kliniken
- Principal Investigator Name
- Ana Carneiro
- Principal Investigator Email
- ana.carneiro@med.lu.se
- Contact Person Name
- Ana Carneiro
- Contact Person Email
- ana.carneiro@med.lu.se
Denmark
- Earliest CTIS Part Ii Submission Date
- 13-03-2026
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 52
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Rigshospitalet
- Department Name
- Department of Oncology, Phase 1 Unit
- Principal Investigator Name
- Martin Hoejgaard
- Principal Investigator Email
- firstname.middlename.lastname@regionh.dk
- Contact Person Name
- Martin Hoejgaard
- Contact Person Email
- firstname.middlename.lastname@regionh.dk
Netherlands
- Earliest CTIS Part Ii Submission Date
- 02-04-2026
- Latest Decision Or Authorization Date
- 11-05-2026
- Processing Time Days
- 39
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Medical Oncology
- Principal Investigator Name
- Eelke Gort
- Principal Investigator Email
- oncostudies@umcutrecht.nl
- Contact Person Name
- Eelke Gort
- Contact Person Email
- oncostudies@umcutrecht.nl
- Site Name
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Principal Investigator Name
- Marieke Vollebergh
- Principal Investigator Email
- fase1secretariaat@nki.nl
- Contact Person Name
- Marieke Vollebergh
- Contact Person Email
- fase1secretariaat@nki.nl
Sponsor
Primary sponsor
- Full Name
- Glaxosmithkline Research & Development Limited
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United Kingdom
Contract research organisations
- Name
- Sermes CRO
- Responsibilities
- patient fee reimbursement
- Name
- Pharmaceutical Product Development LLC
- Responsibilities
- 4
- Name
- Bioclinica Inc.
- Responsibilities
- Clario - Medical and Ophthalmology Imaging
- Name
- Eresearchtechnology Inc.
- Responsibilities
- Clario - Cardiac Safety Services
- Name
- Evidera Inc.
- Responsibilities
- 7
Third parties
- {"country":"United States","full_name":"Evidera Inc.","duties_or_roles":"7","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Clario - Medical and Ophthalmology Imaging","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Medable Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"medicine product destruction","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long Term Storage","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Fm Richard Et Associes","duties_or_roles":"Reimbursement of patient fees and compensation. Payment of biological examens performed outside the sites.","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Clario - Cardiac Safety Services","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient Travel and payments","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long Term Storage","organisation_type":"Pharmaceutical company"}
- {"country":"Spain","full_name":"Sermes CRO","duties_or_roles":"patient fee reimbursement","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Neogenomics Inc.","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- GSK5460025
- Active Substance
- GSK5460025A
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL USE
- Authorisation Status
- prodAuthStatus: 1
- First In Human
- Yes
- Investigational Product Name
- GSK5460025
- Active Substance
- GSK5460025A
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL USE
- Authorisation Status
- prodAuthStatus: 1
- First In Human
- Yes
- Investigational Product Name
- GSK5460025
- Active Substance
- GSK5460025A
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL USE
- Authorisation Status
- prodAuthStatus: 1
- First In Human
- Yes
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