A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer

Adequate organ and bone marrow function within 14 days before the day of first dosing as defined in the protocol

Left ventricular ejection fraction ≥ 50% within 28 days before enrollment

Negative pregnancy test (serum) for women of childbearing potential

Known or suspected leptomeningeal disease

Prior exposure to tucatinib treatment

Refractory nausea and vomiting, chronic gastrointestinal disease, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of T-DXd

History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence

Based on screening contrast brain MRI/CT scan, participants must not have any of the following: any untreated brain lesions \> 2.0 cm in size; ongoing use of systemic corticosteroids for control of symptoms of BMs; any brain lesion thought to require immediate local therapy; have poorly controlled (\> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to BMs not withstanding CNS-directed therapy

Has spinal cord compression

Known active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. Participants with past or resolved hepatitis B virus infection are eligible, if negative for hepatitis B surface antigen and positive for anti-hepatitis B core antigen

Participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA

Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals

Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd

Participants with a medical history of myocardial infarction within 6 months before screening, symptomatic congestive heart failure (New York Heart Association Class II to IV)

History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening

Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue or inflammatory disorders

Prior exposure, without adequate treatment washout period before the day of first dosing, to chloroquine/hydroxychloroquine: \< 14 days

Anticancer chemotherapy: immunotherapy (non-antibody-based therapy), retinoid therapy, hormonal therapy: \< 3 weeks

\< 6 weeks for nitrosoureas or mitomycin

Antibody-based anticancer therapy: \< 4 weeks

Any concurrent anticancer treatment. Concurrent use of hormonal therapy for noncancer- related conditions is allowed

Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline

Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation, radiation to the chest, or to more than 30% of the bone marrow within 4 weeks before the first dose of study intervention

Participants with prior exposure to immunosuppressive medication within 14 days prior to first study dose

Participants with a known hypersensitivity to study intervention or any of the excipients of the product or other monoclonal antibodies

What this study is about