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

Prior treatment

• 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 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.

Other illness

• History of known hypersensitivity to planned study treatment
• Known to be positive for Hepatitis B or C

• 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.