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

A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers

This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer. It will also look at whether tucatinib works with these drugs to treat certain types of cancer.

The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach, intestines, or gallbladder (gastrointestinal cancer).

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-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.