This study will check how well a new medicine, Risvutatug rezetecan, (Ris-Rez, also known as 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.
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).
Has histologically confirmed unresectable, locally advanced or unresectable metastatic adenocarcinoma of the colon or rectum (histology defined by World Health Organization (WHO) classification).
Has histologically or cytologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the pancreas (histology defined by WHO classification).
Is willing to use adequate contraception.
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 or first dose of study intervention, depending on sub-cohort/cohort assignment
Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
Has severe, uncontrolled or active cardiovascular disorders.
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Treatment groupsSee each treatment group below.