Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer
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
- Metastatic Colorectal Adenocarcinoma
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 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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned 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. |
|
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. |
|
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. |
|
More Details
- Status
- Completed
- Sponsor
- Seagen Inc.