HER2+ Metastatic Colorectal Cancer MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Seattle Genetics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically and/or cytologically documented adenocarcinoma of the colon or rectum, which is metastatic and/or unresectable - Unless contraindicated, subjects 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 mCRC after 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 - Subjects must be 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 lesion is required - 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: a. HER2+ overexpression (3+ immunohistochemistry [IHC]) by an FDA-approved HER2 IHC test b. HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved HER2 in situ hybridization assay c. 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 subject has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation - Have an 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 obtained =7 days prior to the first study treatment Other protocol-defined inclusion criteria may apply. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - Previous treatment with anti-HER2 targeting therapy - Previous treatment with any systemic anticancer therapy, non-central nervous system radiation, or experimental agent =3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial - Have any 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 course of the study - Serious, non-healing wound, ulcer, or bone fracture - Known to be positive for hepatitis B by surface antigen expression, HIV or to have active hepatitis C infection - 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 a 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 - Have any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures - 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 - Subjects with known active CNS metastasis Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the antitumor activity of tucatinib given in combination with trastuzumab, in Cohorts A+B, as measured by confirmed objective response rate (cORR, per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria), according to blinded independent central review (BICR) assessment;Secondary Objective: •To evaluate antitumor activity of tucatinib in combination with trastuzumab, in Cohorts A+B, by ORR by 12 weeks of treatment (RECIST 1.1), according to BICR assessment •To evaluate antitumor activity of tucatinib monotherapy, in Cohort C, as measured by ORR by 12 weeks of treatment (RECIST 1.1), according to BICR assessment •To assess DOR in subjects treated with tucatinib in combination with trastuzumab (RECIST 1.1), in Cohorts A+B, according to BICR assessment •To assess DOR in subjects treated with tucatinib monotherapy (RECIST 1.1), in Cohort C, according to BICR assessment •To assess PFS in subjects treated with tucatinib in combination with trastuzumab (RECIST 1.1), in Cohorts A+B, according to BICR assessment •To assess OS in subjects treated with tucatinib in combination with trastuzumab, in Cohorts A+B •To assess safety and tolerability of tucatinib in combination with trastuzumab, in Cohorts A+B •To assess safety and tolerability of tucatinib monotherapy, in Cohort C;Primary end point(s): cORR (confirmed complete response [CR] or partial response [PR]), per RECIST 1.1, according to BICR assessment, in pooled Cohorts A+B;Timepoint(s) of evaluation of this end point: Up to 8 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ORR (RECIST 1.1) by 12 weeks of treatment, according to BICR assessment • DOR (RECIST 1.1), according to BICR assessment • PFS (RECIST 1.1), according to BICR assessment, in Cohorts A+B • OS, in Cohorts A+B • Frequency and severity, according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria, of all treatment-emergent adverse events (TEAEs) and treatment-related TEAEs • Frequency of serious adverse events (SAEs) and deaths due to adverse events (AEs) • Frequency of treatment modifications and permanent treatment discontinuations due to AEs • Frequency and severity of laboratory abnormalities;Timepoint(s) of evaluation of this end point: • ORR: up to 12 weeks • DOR: Up to approximately 4 years • PFS in Cohorts A+B: Up to approximately 4 years • OS in Cohorts A+B: Up to approximately 4 years • Frequency and severity, according to CTCAE v4.03 criteria, of all TEAEs and treatment-related TEAEs: Through 30 days following last dose; up to approximately 9 months overall per subject • Frequency of SAEs and deaths due to AEs: Through 30 days following last dose; up to approximately 9 months overall per subject • Frequency of treatment modifications and permanent treatment discontinuations due to AEs: Through 30 days following last dose; up to approximately 9 months overall per subject • Frequency and severity of laboratory abnormalities: Through 30 days following last dose; up to approximately 9 months overall per subject | — |
Countries
Belgium, France, Italy, Spain, United States
Contacts
Public ContactSeagen Clinical Trial Information
Seattle Genetics, Inc.
Outcome results
None listed