RWF_SGNTUC-025

A Single Arm, Open Label Phase 2 Study of Tucatinib in Combination with Trastuzumab Deruxtecan in Subjects with Previously Treated Unresectable Locally-Advanced or Metastatic HER2+ Breast Cancer

This trial studies how well the drug tucatinib works when given with trastuzumab deruxtecan. It will also look at what side effects happen when these drugs are given together. A side effect is anything a drug does besides treating cancer.
Participants in this trial have HER2-positive (HER2+) breast cancer that has either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable). All participants will get both tucatinib and trastuzumab deruxtecan.

Inclusion Criteria:
• Have confirmed HER2+ breast cancer, as defined by the current American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines, previously determined at a Clinical Laboratory Improvements Amendments (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory.
• Have received 2 or more prior anti-HER2-based regimens in the metastatic setting
• Have progression of unresectable LA/M breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy
• Have measurable disease assessable by RECIST v1.1
• CNS Inclusion - Based on medical history and screening contrast brain magnetic resonance imaging (MRI), participants with a history of brain metastases must have one of the following:
o Untreated brain metastases not needing immediate local therapy. For participants with untreated central nervous system (CNS) lesions >2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment
o Previously treated brain metastases

Exclusion Criteria:
• Have previously been treated with:
o Lapatinib or neratinib within 12 months of starting study treatment (except in cases where lapatinib or neratinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity)
o Tucatinib or enrolled on a tucatinib clinical trial
o Any investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) (eg, afatinib) at any time previously
o Trastuzumab deruxtecan or another antibody-drug conjugate (ADC) consisting of an exatecan derivative
• Have received treatment with:
o Any systemic anti-cancer therapy (including hormonal therapy) or experimental agent ≤21 days of first dose of study treatment or are currently participating in another interventional clinical trial. An exception for the washout of hormonal therapies is gonadotropin releasing hormone (GnRH) agonists used for ovarian suppression in premenopausal women, which are permitted concomitant medications
o Treatment with non-CNS radiation ≤7 days prior to first dose of study treatment
o Major surgery <28 days of first dose of study treatment
• Have clinically significant cardiopulmonary disease (such as history of iterstitial lung disease (ILD)/pneumonitis that required systemic corticosteroids, or have current ILD/pneumonitis, or where suspected ILD /pneumonitis cannot be ruled out be imaging at screening)
• Have known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment
• Presence of known chronic liver disease
Phase II
NCT04539938
Oncology
Breast
Alison Conlin, M.D.
Seagen Inc. (formerly Seattle Genetics, Inc.)
Nikki Moxon
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Clackamas Clinic
  • Providence Cancer Institute Franz Clinic
  • Providence Cancer Institute Newberg Clinic