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 is histologically 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 of their 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 as determined by the investigator
Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by the investigator
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-immunotherapy-drugs-are-boosting-survival/" >PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a 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.