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

For people ages 18-100

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 Anvumetostat.
• 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.