The STOP-HER2 Trial: A Phase 2 Study of Stopping Trastuzumab - Outcomes in Patients with HER2+ Metastatic Breast Cancer

This study is being done to see if anti-HER2 treatment be safely stopped in patients with
HER2-positive metastatic breast cancer (MBC) that have had exceptional response to treatment.
Exceptional response" is considered as cancer progression being controlled for three years or
more since starting anti-HER2 treatment.

Inclusion Criteria:

- Age ≥18 years

- Participants must have histologically or cytologically confirmed unresectable locally
advanced or metastatic invasive breast carcinoma that is HER2-positive by American
Society of Clinical Oncology/College of American Pathologists 2018 criteria, as
assessed by standard institutional guidelines (central testing is not required). Both
estrogen receptor (ER)-positive/HER2-positive and ER-negative/HER2-positive will be
eligible.

- Participants with ER-positive disease should continue endocrine therapy.

- Participants must be currently receiving first-line anti-HER2 therapy (any regimen)
for metastatic disease and must have been on this therapy for at least 3 years without
evidence of progressive disease according to RECIST 1.1 criteria. The following
exceptions apply:

- Patients with history of brain-only progressive disease previously treated with local
therapy (surgery and/or radiation therapy) are eligible, provided they meet all the
following study criteria:

- Asymptomatic

- Not requiring anti-convulsant for symptomatic control

- Not requiring corticosteroids

- No evidence of interim central nervous system (CNS) progression between the
completion of CNS-directed therapy and screening radiographic study

- Minimum of 2 years (24 months) between completion of CNS-directed therapy and
study start

- Participants with history of oligo-progression (i.e., progressive disease of a single
lesion) outside CNS treated with local treatment and/or change of endocrine therapy
only are eligible, provided they meet the following criteria:

- No evidence of interval progression between completion of local treatment or
endocrine therapy change and screening radiographic study

- Minimum 2 years (24 months) between completion of local therapy or treatment
switch and study start

- CT scan within 30 days of study start without definite evidence of progressive disease
in the opinion of the treating investigator.

- Available, representative archival formalin-fixed paraffin-embedded (FFPE) tumor
tissue block from primary and/or metastatic site. If tissue block is unavailable, 20
unstained 10uM slides will be accepted (less than 20 slides may be acceptable with
documentation of Sponsor-Investigator approval and would not require an eligibility
exception). Tumor tissue must be received by coordinating site prior to study
enrollment.

- ECOG performance status 0-1

- For intervention arm only (cohort 2): willingness to stop anti-HER2 systemic therapy

- Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures

- Ability to understand the study requirements and document informed consent indicating
awareness of the investigational nature and the risks of this study

- Participants with another prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of this trial are eligible

Exclusion Criteria:

- Participants who are receiving any investigational agents to treat breast cancer

- Participants with psychiatric illness/social situations that would limit compliance
with study requirements.

- All English- speaking patients will participate in the PRO measures. Patients that do
not read or understand English are eligible to participate but will be exempt from the
patient completed questionnaires