A Study of Raludotatug Deruxtecan (R-DXd) in People With Gastrointestinal Cancers (MK-5909-005)

Researchers are looking for new ways to treat certain types of advanced gastrointestinal (GI) cancers. The study medicine raludotatug deruxtecan (also called MK-5909, R-DXd, or DS-6000a) is a type of medicine called an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The main goal of this study is to learn if the cancer responds to treatment (gets smaller or goes away).

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has one of the following cancers: * Unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) * Unresectable or metastatic adenocarcinoma of the biliary tract \[intra- or extrahepatic holangiocarcinoma (CCA) or gallbladder cancer (GBC)\] * Unresectable or metastatic colorectal adenocarcinoma * Unresectable or metastatic gastric adenocarcinoma * Gastroesophageal junction adenocarcinoma (GEJAC) * Esophageal adenocarcinoma (EAC) * Has received prior therapy for the cancer * Has a life expectancy of at least 3 months * If human immunodeficiency virus (HIV) infected, must have well controlled HIV on antiretroviral therapy (ART) Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids or has current ILD/pneumonitis, and/or suspected ILD/pneumonitis * Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses * Has uncontrolled or significant cardiovascular disease * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Active autoimmune disease that has required systemic treatment in the past 2 years * Has not adequately recovered from major surgery or has ongoing surgical complications * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease