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

Protocol # :
HER2 Positive Breast Cancer
Disease Sites
Principal Investigator
Lin, Nancy, U
Site Research Nurses
Campbell, Margaret
Caradonna, Lisa
Casella, Allison
Cung, Connie
Dishman, Rachel, C.
Ficociello, Samantha
Jeon, Maryangel, H.
Jeon, Maryangel, H.
Kasparian, Elizabeth
Macauley, Colleen
Orechia, Meghan
Patel, Nikita
Roche, Kathleen, A.
Rutter, Morgan

Trial Description

This trial studies how well the drug tucatinib works when given with trastuzumab deruxtecan
(T-DXd). 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 T-DXd.

Eligibility Requirements

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.

- History of prior treatment with a taxane and trastuzumab in the LA/M setting OR
progressed within 6 months after neoadjuvant or adjuvant treatment, including a taxane
and trastuzumab.

- 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

- Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

- Have a life expectancy of at least 6 months, in the opinion of the investigator

- 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:

- 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

- Previously treated brain metastases

- Brain metastases previously treated with local therapy may either be stable
since treatment or may have progressed since prior local CNS therapy,
provided that there is no clinical indication for immediate re-treatment
with local therapy in the opinion of the investigator

- Participants treated with CNS local therapy for newly identified or
previously treated progressing lesions found on contrast brain MRI performed
during screening for this study may be eligible to enroll if all of the
following criteria are met:

- Time since whole brain radiation therapy (WBRT) is ≥14 days prior to
first dose of study treatment, time since stereotactic radiosurgery
(SRS) is ≥7 days prior to first dose of study treatment, or time since
surgical resection is ≥28 days

- Other sites of measurable disease by RECIST v1.1 are present

- Relevant records of any CNS treatment must be available

Exclusion Criteria

- Have previously been treated with:

- 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)

- Tucatinib or enrolled on a tucatinib clinical trial

- Any investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine
kinase inhibitor (TKI) (eg, afatinib) at any time previously

- Trastuzumab deruxtecan or another antibody-drug conjugate (ADC) consisting of an
exatecan derivative

- Have received treatment with:

- 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

- Treatment with non-CNS radiation ≤7 days prior to first dose of study treatment

- 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

- Have known myocardial infarction or unstable angina within 6 months prior to first
dose of study treatment

- Known to be positive for hepatitis B by surface antigen expression. Known to be
positive for hepatitis C infection. Participants who have been treated for hepatitis C
infection are permitted if they have documented sustained virologic response of 12

- Presence of known chronic liver disease

- Active or uncontrolled clinically serious infection

- Have inability to swallow pills or significant gastrointestinal disease which would
preclude the adequate oral absorption of medications