A Study Evaluating AMG 193 in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion (MTAPESTRY 103)

Inclusion Criteria

• Subprotocol B Inclusion: - Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years). - Histologically or cytologically confirmed diagnosis of metastatic and/or unresectable (locally advanced) adenocarcinoma of the pancreas. - Tumor tissue (FFPE sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before dosing. - Homozygous MTAP-deletion. - Disease measurable as defined by RECIST v1.1. - Adequate organ function as defined in the protocol. Exclusion: - Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor. - Radiation therapy within 28 days of first dose. - Major surgery within 28 days of first dose of AMG 193. - Cardiovascular and pulmonary exclusion criteria as defined in the protocol. - Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis). - History of solid organ transplantation. Subprotocol C Inclusion: - Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years). - Histologically or cytologically confirmed diagnosis of metastatic and/or unresectable (locally advanced) adenocarcinoma of the pancreas. - Homozygous MTAP-deletion. - Rat Sarcoma Viral Oncogene Homolog (RAS) mutation - Received at least 1 prior systemic therapy for advanced or metastatic PDAC. - Disease measurable as defined by RECIST v1.1. - Adequate organ function as defined in the protocol. Exclusion: - Prior treatment with aMAT2A inhibitor, a PRMT5 inhibitor, or a MAPK pathway inhibitor, including KRAS inhibitors. - Cardiovascular and pulmonary exclusion criteria as defined in the protocol. - Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis). - History of solid organ transplantation.