Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with docetaxel as first-line therapy (1L) for patients (pts) with advanced HER2-positive breast cancer (BC): Updated results from a phase 1b/2 study.

1044 Background: Despite HER2-targeted agents improving outcomes in HER2-positive (+) BC, some pts develop resistance, relapse, or do not respond to current 1L therapies. Zani, also known as ZW25, is a novel HER2-targeted bispecific antibody that binds to two distinct extracellular domains of HER2. Preliminary results from this phase 1b/2 trial (NCT04276493) showed that zani plus docetaxel had a manageable safety profile and demonstrated promising antitumor activity in pts with advanced HER2+ BC; here we present the updated data following enrollment completion. Methods: Cohort 1 of this open-label study is evaluating zani in combination with docetaxel as a 1L therapy in adult females with advanced HER2+ BC who may have received prior neoadjuvant/adjuvant therapy. Cohort 1a pts received zani 30 mg/kg intravenously (IV), Cohort 1b pts received zani 1800 mg IV, both with docetaxel 75 mg/m 2 IV every 3 weeks. The primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed duration of response (DoR) and disease control rate (DCR). Results: As of Nov 22, 2022, 37 pts (median age 55.0 years [range: 33-80]) were assigned to Cohort 1a (n=10) or 1b (n=27). Median study follow-up was 15.5 months (range: 1.1-29.3); patients received a median of 13 treatment cycles (range 1-37) and 18 (48.6%) pts remained on treatment. Of the 33 efficacy evaluable (EE) pts, confirmed ORR was 90.9% (95% confidence interval [CI]: 75.7, 98.1). Efficacy data are summarized in Table. In total, 36 (97.3%) pts experienced ≥1 treatment-related adverse event (TRAE); 25 (67.6%) pts experienced ≥grade 3 TRAEs. The most common ≥grade 3 TRAEs were decreased neutrophil count, experienced by 18 (48.6%) pts, and decreased white blood cell count, experienced by 7 (18.9%) pts. Serious TRAEs occurred in 6 (16.2%) pts; no TRAEs led to death. Conclusions: Zani combined with docetaxel demonstrated promising antitumor activity as 1L therapy for advanced HER2+ BC, with a manageable safety profile. Clinical trial information: NCT04276493 . [Table: see text]