132P Neoadjuvant zanidatamab for stage I node-negative HER2- positive breast cancer (BC)

Outcome of patients (pts) w/ stage I node neg HER2+ treated wkly paclitaxel x 12 doses and trastuzumab 1yr is excellent (10yr RFS 96%). Therefore, trials to de-escalate chemo use targeted therapy alone are underway. Zanidatamab a novel, humanized, bispecific, immunoglobulin G isotype 1-like, monoclonal antibody directed against the juxtamembrane extracellular domain (ECD4) dimerization (ECD2) HER2. This results in HER2 clustering that modulates signaling leads immune activation. demonstrated antitumor activity heavily pre-treated metastatic BC with acceptable safety profile. We hypothesized zanidatamab would be safe effective regimen for women BC. Pts 1-3cm, clinically were enrolled this investigator-initiated clinical trial. had BC: 3+ by IHC or 2+ ISH +. received 2-wkly zani x6 prior surgery. ER+ tumors also neoadjuvant endocrine therapy: postmenopausal pts letrozole 2.5mg daily, premenopausal tamoxifen 20mg daily GNRH on treating physician preference. The primary objective was evaluate efficacy as determined pathologic complete response (pCR). Secondary objectives included residual cancer burden (RCB), radiological response, profile zanidatamab. Eleven enrolled. Median age 61yrs old (range 30-72). tumor size 2.2cm 1-3cm). Four pre-menopausal. Six >2cm tumors. Three 3 letrozole. All completed 6 cycles Sx. (36%) pCR, RCB1 (28%) 4 RCB2 (36%). met success criterion Simon’s design (>=3/17 pCR) targeting 25% pCR rate 5% null rate. Treatment tolerated well. There no grade toxicities. One pt minor infusion-related reaction 2 acne, 1 diarrhea. Neoadjuvant months showed significant efficacy, (pCR/RCB-1 64%) trial ongoing has been modified increase treatment duration 5mths (10 cycles).