Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 recent 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 laboratory, meeting at least one of the following criteria:
  • HER2+ overexpression (3+ immunohistochemistry [IHC])by an FDA-approved HER2 ICH test
  • HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH]))
  • HER2 (ERBB2) amplification by CLIA-certified 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

o 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 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.

o Exceptions are malignancies with a negligible risk of metastasis or death

- Subjects with known active CNS metastasis o 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort A: Tucatinib + Trastuzumab
Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
  • Drug: Trastuzumab
    Given intravenously (into the vein; IV)
    Other names:
    • Herceptin
  • Drug: Tucatinib
    Given orally
    Other names:
    • ARRY-380
    • ONT-380
Experimental
Cohort B: Tucatinib + Trastuzumab
Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
  • Drug: Trastuzumab
    Given intravenously (into the vein; IV)
    Other names:
    • Herceptin
  • Drug: Tucatinib
    Given orally
    Other names:
    • ARRY-380
    • ONT-380
Experimental
Cohort C: Tucatinib Monotherapy
Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
  • Drug: Tucatinib
    Given orally
    Other names:
    • ARRY-380
    • ONT-380

Recruiting Locations

University of Kansas Cancer Center
Westwood, Kansas 66205
Contact:
Kayra Thompson
913-588-6029
kthompson8@kumc.edu

More Details

Status
Recruiting
Sponsor
Seattle Genetics, Inc.

Study Contact

Seattle Genetics Trial Information Support
866-333-7436
clinicaltrials@seagen.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.