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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06885034




Registration number
NCT06885034
Ethics application status
Date submitted
13/03/2025
Date registered
19/03/2025
Date last updated
15/09/2025

Titles & IDs
Public title
A Study to Test the Safety and Effectiveness of GSK5764227, Alone or With Other Treatments, in Participants With Advanced Gastrointestinal Cancers That Cannot be Surgically Removed
Scientific title
A Phase 1b/2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of GSK5764227 Alone and in Combination in Participants With Previously Treated Advanced Unresectable or Metastatic Gastrointestinal Solid Tumors
Secondary ID [1] 0 0
2025-520672-26
Secondary ID [2] 0 0
223675
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - GSK5764227

Experimental: CRC-A: GSK5764227 (Dose 1) -

Experimental: CRC-A: GSK5764227 (Dose 2) -

Experimental: CRC-B: GSK5764227 (Dose 3) -

Experimental: CRC-B: GSK5764227 (Dose 4) -

Experimental: PDAC: GSK5764227 (Dose 5) -


Treatment: Other: GSK5764227
GSK5764227 will be administered

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Confirmed Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 22 months
Secondary outcome [1] 0 0
Unconfirmed ORR
Timepoint [1] 0 0
Up to approximately 37 months
Secondary outcome [2] 0 0
Duration of Response (DoR)
Timepoint [2] 0 0
Up to approximately 37 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
Up to approximately 37 months
Secondary outcome [4] 0 0
Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity
Timepoint [4] 0 0
Up to approximately 37 months
Secondary outcome [5] 0 0
Number of participants with AEs leading to dose modifications, discontinuation of study interventions or death
Timepoint [5] 0 0
Up to approximately 37 months
Secondary outcome [6] 0 0
Changes from baseline in vital signs: Temperature (degree Celsius)
Timepoint [6] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [7] 0 0
Changes from baseline vital signs: Respiratory rate (breaths per minute)
Timepoint [7] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [8] 0 0
Changes from baseline vital signs: Pulse rate (beats per minute)
Timepoint [8] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [9] 0 0
Changes from baseline vital signs: Blood pressure [millimetres of mercury (mmHg)
Timepoint [9] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [10] 0 0
Changes from baseline in hematology parameters: [White blood cell count (WBCs per microliter)
Timepoint [10] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [11] 0 0
Changes from baseline in hematology parameters: [Haemoglobin (Hgb) (grams per deciliter)
Timepoint [11] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [12] 0 0
Changes from baseline in hematology parameters:[Haematocrit (Proportion of red blood cells in blood)
Timepoint [12] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [13] 0 0
Changes from Baseline haematology parameter: [Red Blood Cell Count (RBC) (million cells per microliter)
Timepoint [13] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [14] 0 0
Changes from baseline haematology parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per liter)
Timepoint [14] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [15] 0 0
Changes from Baseline haematology parameter: Platelet count (cells per microliter)
Timepoint [15] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [16] 0 0
Changes from baseline Clinical chemistry parameters: Total Protein, Albumin (Grams per deciliter)
Timepoint [16] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [17] 0 0
Changes from baseline Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per liter)
Timepoint [17] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [18] 0 0
Changes from baseline Clinical Chemistry parameters: Total Bilirubin and Direct Bilirubin, Glucose, Calcium, Potassium, Sodium, Magnesium, Urea Nitrogen or urea, and Creatinine (milligrams per deciliter)
Timepoint [18] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [19] 0 0
Changes from baseline Clinical Chemistry parameters: Lactate dehydrogenase, Amylase and Lipase (units per liter)
Timepoint [19] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [20] 0 0
Changes from baseline Clinical Chemistry parameters: Chloride (millimoles per liter)
Timepoint [20] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [21] 0 0
Changes from baseline Clinical Chemistry parameters: Creatinine clearance (milliliters per minute)
Timepoint [21] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [22] 0 0
Changes from baseline cardiac function: Electrocardiogram (ECG) (milliseconds)
Timepoint [22] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [23] 0 0
Changes from baseline Eastern Cooperative Oncology Group performance status (ECOG-PS)
Timepoint [23] 0 0
Baseline (Day 1) and up to approximately 37 months
Secondary outcome [24] 0 0
Maximum observed concentration (Cmax) of GSK5764227 (conjugated antibody) and GSK5757810 (small molecule toxin)
Timepoint [24] 0 0
Up to approximately 37 months
Secondary outcome [25] 0 0
Time to reach Cmax (Tmax) of GSK5764227 (conjugated antibody) and GSK5757810 (small molecule toxin)
Timepoint [25] 0 0
Up to approximately 37 months
Secondary outcome [26] 0 0
Area under the concentration-time curve (AUC) of GSK5764227 (conjugated antibody) and GSK5757810 (small molecule toxin)
Timepoint [26] 0 0
Up to approximately 37 months
Secondary outcome [27] 0 0
Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb)
Timepoint [27] 0 0
Up to approximately 37 months
Secondary outcome [28] 0 0
Titers of ADA against GSK5764227
Timepoint [28] 0 0
Up to approximately 37 months
Secondary outcome [29] 0 0
Number of participants with symptomatic AEs, by severity, as measured by Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Timepoint [29] 0 0
Up to approximately 37 months
Secondary outcome [30] 0 0
Level of bother of AEs as measured by Functional Assessment of Cancer Therapy - Item GP5 (FACT-GP5)
Timepoint [30] 0 0
Up to approximately 37 months

Eligibility
Key inclusion criteria
Inclusion criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

• Is at least 18 or the legal age of consent in the jurisdiction in which the study is taking place years of age at the time of signing the informed consent form (ICF).

CRC Cohort

* Has histologically confirmed unresectable/, locally advanced or unresectable metastatic adenocarcinoma of the colon or rectum (histology defined by World Health Organization (WHO) classification).
* Must have received at least 1 and no more than 2 lines of systemic treatment for advanced colorectal cancer (CRC), with documented progression on most recent prior line of therapy.
* Must provide tumor tissue from a newly obtained fresh biopsy or an archival tumor tissue.

PDAC Cohort

* Has histologically or cytologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the pancreas (histology defined by WHO classification).
* Must have received 1 and no more than 1 line of therapy for advanced PDAC, with documented progression.
* Should provide tumor tissue at screening, where available or medically feasible.

All Cohorts

* Has at least 1 target lesion per RECIST 1.1, as determined by the investigator.
* Is willing to use adequate contraception.
* Is capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in the protocol.
* Has an ECOG performance status of 0 or 1.
* Has adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

Participants are excluded from the study if any of the following criteria apply:

* Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas [e.g., breast, cervix, bladder] that have been resected with no evidence of disease.
* Has had any major surgery within 28 days prior to randomization (CRC Cohort) or first dose of study intervention (PDAC Cohort).
* Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
* Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
* Has severe, uncontrolled or active cardiovascular disorders.
* Has serious or poorly controlled hypertension.
* Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
* Has serious infection within 4 weeks prior to the first dose.
* Known active infectious diseases requiring systemic treatment or known Human immunodeficiency virus (HIV).
* Has serious arteriovenous thromboembolic events (such as deep vein thrombosis, pulmonary embolism, etc.) within 3 months prior to the first dose.
* Has untreated brain or Central nervous system (CNS) metastases or brain/CNS metastases that have progressed.
* Has current active pneumonitis or any history of pneumonitis requiring steroids or immunomodulatory treatment within 90 days of planned [randomization] or any history of drug-induced pneumonitis.
* Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening.
* Has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition that could affect the participant's safety).
* Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to Grade 1 or to the baseline status preceding prior therapy.
* Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures.
* Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
* Has documented presence of Hepatitis B surface antigen (HBsAg) or HBcAb at screening or within 3 months prior to the first dose of study intervention.
* Has a positive Hepatitis C virus (HCV) antibody test result at screening or within 3 months prior to the first dose of study intervention.
* Has a positive HCV RNA test result at screening or within 3 months prior to the first dose of study intervention.
* Has received immunosuppressive agents within 30 days prior to first dose of study intervention (or requires long-term [30 days or longer]).
* Has received any prior therapy with an Antibody-drug conjugate (ADC) with a Topoisomerase-1 (TOPO1)-inhibitor payload.
* Has received any live vaccine within 30 days of randomization (CRC Cohort) or before first dose of study intervention (PDAC Cohort).
* Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of interventional medical research and/or has received treatment with any anticancer or investigational agent within 4 weeks prior to randomization.
* Is pregnant or breastfeeding.
* Is unable to adhere to the protocol defined SoA, including requirements for the Follow-up Period of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
United States of America
State/province [2] 0 0
Washington
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec
Country [5] 0 0
Japan
State/province [5] 0 0
Hokkaido
Country [6] 0 0
Japan
State/province [6] 0 0
Osaka
Country [7] 0 0
Japan
State/province [7] 0 0
Tokyo
Country [8] 0 0
South Korea
State/province [8] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.