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Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

Trial Status: Active

This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body. In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.

Inclusion Criteria

  • Histologically and/or cytologically documented adenocarcinoma of the colon or rectum that is metastatic and/or unresectable
  • Unless contraindicated, participants must have received and failed regimens containing the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins or is MSI-High.
  • Have progression of unresectable or metastatic CRC after the last systemic therapy, or be intolerant of last systemic therapy
  • Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS testing
  • Willing and able to provide the most recently available tissue blocks obtained prior to treatment initiation. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor
  • Have confirmed HER2-positive mCRC, as defined by having tumor tissue tested at a Clinical Laboratory Improvement Act (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory, meeting at least one of the following criteria:
  • HER2+ overexpression (3+ immunohistochemistry [IHC]) by an FDA-approved or Conformité Européene (CE)-marked HER2 ICH test
  • HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved or CE-marked HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH]))
  • HER2 (ERBB2) amplification by CLIA-certified or ISO-accredited next generation sequencing (NGS) sequencing assay
  • Have radiographically measurable disease assessable by RECIST 1.1, with at least one site of disease that is measurable and that has not been previously irradiated; or, if the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
  • Life expectancy greater than 3 months
  • Have adequate hematological, hepatic, renal, coagulation, and cardiac function

Exclusion Criteria

  • Previous treatment with anti-HER2 targeting therapy
  • Previous treatment with any systemic anticancer therapy, non-central nervous system radiation, or experimental agent within 3 weeks of first dose of study treatment
  • Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
  • Alopecia and neuropathy, which must have resolved to ≤ Grade 2
  • Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely
  • Anemia, which must have resolved to ≤ Grade 2
  • Decreased ANC, which must have resolved to ≤ Grade 2
  • Have clinically significant cardiopulmonary disease
  • Have known myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment
  • Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or anticipation of need for major surgical procedure during the study
  • Serious, non-healing wound, ulcer, or bone fracture
  • Known to be positive for hepatitis B by surface antigen expression
  • Known to have active hepatitis C infection
  • Exception for participants with a documented sustained virologic response of 12 weeks
  • Known to be positive for human immunodeficiency virus (HIV)
  • Subjects who are pregnant, breastfeeding, or planning a pregnancy
  • Inability to swallow pills or any significant gastrointestinal disease which would preclude the adequate oral absorption of medications
  • Have used strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a strong CYP2C8 or CYP3A4 inducer within 5 days prior to first dose of study treatment
  • History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.
  • Exceptions are malignancies with a negligible risk of metastasis or death
  • Subjects with known active CNS metastasis
  • Irradiated or resected lesions are permitted, provided the lesions are fully treated and inactive, subject is asymptomatic, and no steroids have been administered for at least 30 days

Arizona

Phoenix
Mayo Clinic Hospital in Arizona
Status: ACTIVE
Scottsdale
Mayo Clinic in Arizona
Status: ACTIVE
Contact: Theresa Araque
Phone: 480-301-2048

California

Los Angeles
Los Angeles County-USC Medical Center
Status: ACTIVE
Contact: Charlean Ketchens
Phone: 323-865-3035
USC / Norris Comprehensive Cancer Center
Status: ACTIVE
Contact: Charlean Ketchens
Phone: 323-865-3035
Newport Beach
Hoag Memorial Hospital
Status: ACTIVE
Contact: Cristina de Leon
Phone: 949-764-5543

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: ACTIVE

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: ACTIVE

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: IN_REVIEW
Contact: Kati Lyn Dendler
Phone: 317-278-6475

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: ACTIVE

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE

Minnesota

Rochester
Mayo Clinic in Rochester
Status: ACTIVE
Contact: Lucas Michael Hamann
Phone: 507-284-0923

New York

Buffalo
Roswell Park Cancer Institute
Status: ACTIVE
New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Andrea Cercek
Phone: 212-639-8795

North Carolina

Durham
Duke University Medical Center
Status: ACTIVE
Contact: Ireka M. Burrus
Phone: 919-668-1861

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: ACTIVE

Oregon

Portland
OHSU Knight Cancer Institute
Status: ACTIVE

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: ACTIVE

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Seagen Inc.

  • Primary ID SGNTUC-017
  • Secondary IDs NCI-2020-01033, ACCRU-GI-1617, NCI-2017-01107, P30CA015083
  • Clinicaltrials.gov ID NCT03043313