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

What this study is about

This study will check how well a new medicine, GSK5764227, works, how safe it is and how the body handles it in participants all around the world with advanced inoperable or metastatic gastrointestinal cancer who have previously received treatment.

Who can join (things the study team will check)

✅ You may be able to join if…

• 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.

🚫 You may not be able to join if…

• 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.

+ 6 more criteria — see the full checklist in the app.

Where this trial is running

• GSK Investigational Site, Los Alamitos, California, United States
• GSK Investigational Site, Los Angeles, California, United States
• GSK Investigational Site, Santa Monica, California, United States
• GSK Investigational Site, Whittier, California, United States
• GSK Investigational Site, Aurora, Colorado, United States
• GSK Investigational Site, New York, New York, United States
• GSK Investigational Site, New York, New York, United States
• GSK Investigational Site, Durham, North Carolina, United States
• GSK Investigational Site, Houston, Texas, United States
• GSK Investigational Site, San Antonio, Texas, United States
• GSK Investigational Site, Wenatchee, Washington, United States
• GSK Investigational Site, Madison, Wisconsin, United States

+ 73 more sites.

Who to contact

US GSK Clinical Trials Call Center · 877-379-3718 · GSKClinicalSupportHD@gsk.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT06885034.