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Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy for HER2+ Gastrointestinal Cancers

Trial Status: Active

This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (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 unresectable or metastatic solid malignancy that is histologically or cytologically confirmed to be one of the tumor types listed below:
  • CRC
  • Gastric adenocarcinoma
  • GEJ adenocarcinoma
  • Esophageal adenocarcinoma
  • Cholangiocarcinoma
  • Gallbladder carcinoma
  • Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment.
  • Participants in phase 1b cohorts or in Cohort 2B can be receiving an oxaliplatin-based regimen
  • For phase 1b cohorts utilizing FOLFOX: up to 2 cycles of FOLFOX (≤85 mg/m2 oxaliplatin per 2-week cycle) may have been received prior to Cycle 1 Day 1 of study treatment
  • For phase 1b cohorts utilizing CAPOX: up to 2 cycles of FOLFOX (≤85 mg/m2 oxaliplatin per 2-week cycle) or one cycle of CAPOX (≤130 mg/m2 oxaliplatin per 3-week cycle) may have been received prior to Cycle 1 Day 1 of study treatment.
  • For all phase 1b cohorts: if subject has received oxaliplatin in prior cycles at higher doses than those listed above, there must be a minimum of 28 days off treatment prior to Cycle 1 Day 1 of treatment in this study.
  • For Cohort 2B prior to the first dose of study treatment:
  • Subjects may have received up to 1 cycle of FOLFOX (≤85 mg/m2 oxaliplatin per 2-week cycle) prior to Cycle 1 Day 1 but may not have received prior oxaliplatin for metastatic disease
  • Oxaliplatin received in an adjuvant setting is permitted if >6 months prior to Cycle 1 Day 1
  • At least 21 days must have elapsed from prior systemic anticancer therapy (including hormonal and biologic therapy but excluding 1 cycle of FOLFOX), non-central nervous system radiation, and treatment with other experimental agents
  • HER2+ disease, as determined by laboratory testing based on one of the following:
  • For CRC, cholangiocarcinoma, and gallbladder carcinoma:
  • HER2 amplification or overexpression from fresh or archival tumor tissue utilizing one of the following Clinical Laboratory Improvement Amendments (CLIA) certified or International Organization for Standardization (ISO) tests:
  • HER2 overexpression (3+ immunohistochemistry [IHC])
  • HER2 (ERBB2) amplification by in situ hybridization assay (fluorescence in situ hybridization [FISH] or chromogenic in situ hybridization signal ratio ≥2.0 or gene copy number >6)
  • HER2 (ERBB2) amplification by next generation sequencing (NGS) assay
  • HER2 amplification in a CLIA certified blood-based NGS assay
  • Gastric, GEJ, and esophageal adenocarcinomas must use the following criteria:
  • HER2+ overexpression (IHC3+) by an FDA approved assay, from a newly obtained biopsy or surgical specimen, evaluated following the package insert's interpretational manual for gastric adenocarcinoma. IHC2+ is eligible if the tumor is HER2 amplified by an FDA approved in situ hybridization assay
  • 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 oxaliplatin, fluoropyrimidines, leucovorin, trastuzumab, or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 infusion related reactions to oxaliplatin or trastuzumab that were successfully managed, or known allergy to any of the excipients in the study drugs
  • Treatment with oxaliplatin dose in excess of the limitations specified in the inclusion criteria


Mayo Clinic in Arizona
Status: ACTIVE


Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE


University of Colorado Hospital
Status: ACTIVE


Iowa City
University of Iowa / Holden Comprehensive Cancer Center


Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE


Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

North Carolina

Duke University Medical Center


Case Comprehensive Cancer Center
Status: ACTIVE


Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Seagen Inc.

  • Primary ID SGNTUC-024
  • Secondary IDs NCI-2020-05784
  • ID NCT04430738