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.
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.
Has histologically or cytologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the pancreas (histology defined by WHO classification).
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.