Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers

Inclusion Criteria:

• Participants must have an unresectable or metastatic solid malignancy that ishistologically or cytologically confirmed to be one of the tumor types listed below:

• Cohorts 1A, 1B, 1C, and 1D

• CRC

• Gastric adenocarcinoma

• GEJ adenocarcinoma

• Esophageal adenocarcinoma

• Cholangiocarcinoma

• Gallbladder carcinoma

• Cohorts 1E, 1F, 1G, and 2A

• Gastric adenocarcinoma

• GEJ adenocarcinoma

• Esophageal adenocarcinoma

• Cohort 2B

• CRC

• Participants must be candidates to receive an oxaliplatin-based regimen as part oftheir standard-of-care treatment for all cohorts, except Cohort 1G.

• HER2+ disease, as determined by historic or local laboratory testing

• Phase 1b cohorts: measurable or non-measurable disease according to RECIST v1.1 asdetermined by the investigator

• Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by theinvestigator

• Eastern Cooperative Oncology Group Performance Status score of 0 or 1.

Exclusion Criteria:

• History of known hypersensitivity to planned study treatment

• Known to be positive for Hepatitis B or C

• For Cohorts 2A and 2B: prior anti-HER2 therapies

• For Cohorts 1E, 1F, 1G, 2A: Prior therapy with an anti-PD-1, anti-PD-L1, or anti PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cellreceptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due toa Grade 3 or higher immune-related adverse event (irAE)

There are additional inclusion criteria. The study center will determine if criteria for participations are met.